Antiscience

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Antiscience

Antiscience is a set of attitudes and a form of anti-intellectualism that involves a rejection of science and the scientific method. People holding antiscientific views do not accept science as an objective method that can generate universal knowledge. Antiscience commonly manifests through rejection of scientific ideas such as climate change and evolution and the effectiveness of vaccination. It also includes pseudoscience, methods that claim to be scientific but reject the scientific method. Antiscience can lead to belief in false conspiracy theories and alternative medicine. Lack of trust in science has been linked to the promotion of political extremism, corruption and distrust in medical treatments.

History

In the early days of the Scientific Revolution, scientists such as Robert Boyle (1627–1691) found themselves in conflict with those such as Thomas Hobbes (1588–1679), who were skeptical of whether science was a satisfactory way to obtain genuine knowledge about the world.

Hobbes' stance is regarded by Ian Shapiro as an antiscience position:

In his Six Lessons to the Professors of Mathematics,...[published in 1656, Hobbes] distinguished 'demonstrable' fields, as 'those the construction of the subject whereof is in the power of the artist himself,' from 'indemonstrable' ones 'where the causes are to seek for.' We can only know the causes of what we make. So geometry is demonstrable, because 'the lines and figures from which we reason are drawn and described by ourselves' and 'civil philosophy is demonstrable, because we make the commonwealth ourselves.' But we can only speculate about the natural world, because 'we know not the construction, but seek it from the effects.'

In his book Reductionism: Analysis and the Fullness of Reality, published in 2000, Richard H. Jones wrote that Hobbes "put forth the idea of the significance of the nonrational in human behaviour". Jones goes on to group Hobbes with others he classes as "antireductionists" and "individualists", including Wilhelm Dilthey (1833–1911), Karl Marx (1818–1883), Jeremy Bentham (1748–1832) and J S Mill (1806–1873), later adding Karl Popper (1902–1994), John Rawls (1921–2002), and E. O. Wilson (1929–2021) to the list.

Jean-Jacques Rousseau, in his Discourse on the Arts and Sciences (1750), claimed that science can lead to immorality. "Rousseau argues that the progression of the sciences and arts has caused the corruption of virtue and morality" and his "critique of science has much to teach us about the dangers involved in our political commitment to scientific progress, and about the ways in which the future happiness of mankind might be secured". Nevertheless, Rousseau does not state in his Discourses that sciences are necessarily bad, and states that figures like René Descartes, Francis Bacon, and Isaac Newton should be held in high regard. In the conclusion to the Discourses, he says that these (aforementioned) can cultivate sciences to great benefit, and that morality's corruption is mostly because of society's bad influence on scientists.

William Blake (1757–1827) reacted strongly in his paintings and writings against the work of Isaac Newton (1642–1727), and is seen as being perhaps the earliest (and almost certainly the most prominent and enduring) example of what is seen by historians as the aesthetic or Romantic antiscience response. For example, in his 1795 poem "Auguries of Innocence", Blake describes the beautiful and natural robin redbreast imprisoned by what one might interpret as the materialistic cage of Newtonian mathematics and science. Blake's painting of Newton depicts the scientist "as a misguided hero whose gaze was directed only at sterile geometrical diagrams drawn on the ground". Blake thought that "Newton, Bacon, and Locke with their emphasis on reason were nothing more than 'the three great teachers of atheism, or Satan's Doctrine'...the picture progresses from exuberance and colour on the left, to sterility and blackness on the right. In Blake's view Newton brings not light, but night". In a 1940 poem, W.H. Auden summarises Blake's anti-scientific views by saying that he "[broke] off relations in a curse, with the Newtonian Universe".

One recent biographer of Newton considers him more as a renaissance alchemist, natural philosopher, and magician rather than a true representative of scientific Enlightenment, as popularized by Voltaire (1694–1778) and other Newtonians.

Antiscience issues are seen as a fundamental consideration in the historical transition from "pre-science" or "protoscience" such as that evident in alchemy. Many disciplines that pre-date the widespread adoption and acceptance of the scientific method, such as geometry and astronomy, are not seen as anti-science. However, some of the orthodoxies within those disciplines that predate a scientific approach (such as those orthodoxies repudiated by the discoveries of Galileo (1564–1642)) are seen as being a product of an anti-scientific stance.

Friedrich Nietzsche in The Gay Science (1882) questions scientific dogmatism:

"[...] in Science, convictions have no rights of citizenship, as is said with good reason. Only when they decide to descend to the modesty of a hypothesis, of a provisional experimental point of view, of a regulative fiction, maybe they be granted admission and even a certain value within the realm of knowledge – though always with the restriction that they remain under police supervision, under the police of mistrust. But does this not mean, more precisely considered, that a conviction may obtain admission to science only when it ceases to be a conviction? Would not the discipline of the scientific spirit begin with this, no longer to permit oneself any convictions? Probably that is how it is. But one must still ask whether it is not the case that, in order that this discipline could begin, a conviction must have been there already, and even such a commanding and unconditional one that it sacrificed all other convictions for its own sake. It is clear that Science too rests on a faith; there is no Science 'without presuppositions.' The question whether truth is needed must not only have been affirmed in advance, but affirmed to the extent that the principle, the faith, the conviction is expressed: 'nothing is needed more than truth, and in relation to it, everything else has only second-rate value".

The term "scientism", originating in science studies, was adopted and is used by sociologists and philosophers of science to describe the views, beliefs and behavior of strong supporters of applying ostensibly scientific concepts beyond its traditional disciplines. Specifically, scientism promotes science as the best or only objective means to determine normative and epistemological values. The term scientism is generally used critically, implying a cosmetic application of science in unwarranted situations considered not amenable to application of the scientific method or similar scientific standards. The word is commonly used in a pejorative sense, applying to individuals who seem to be treating science in a similar way to a religion. The term reductionism is occasionally used in a similarly pejorative way (as a more subtle attack on scientists). However, some scientists feel comfortable being labelled as reductionists, while agreeing that there might be conceptual and philosophical shortcomings of reductionism.

However, non-reductionist (see Emergentism) views of science have been formulated in varied forms in several scientific fields like statistical physics, chaos theory, complexity theory, cybernetics, systems theory, systems biology, ecology, information theory, etc. Such fields tend to assume that strong interactions between units produce new phenomena in "higher" levels that cannot be accounted for solely by reductionism. For example, it is not valuable (or currently possible) to describe a chess game or gene networks using quantum mechanics. The emergentist view of science ("More is Different", in the words of 1977 Nobel-laureate physicist Philip W. Anderson) has been inspired in its methodology by the European social sciences (Durkheim, Marx) which tend to reject methodological individualism.

Political

Elyse Amend and Darin Barney argue that while antiscience can be a descriptive label, it is often used as a rhetorical one, being effectively used to discredit one's political opponents. Thus, charges of antiscience are not necessarily warranted.

Left-wing

One expression of antiscience is the "denial of universality and... legitimisation of alternatives" and that the results of scientific findings do not always represent any underlying reality but can merely reflect the ideology of dominant groups within society. Alan Sokal states that this view associates science with the political right and is seen as a belief system that is conservative and conformist, that suppresses innovation, that resists change, and that acts dictatorially. This includes the view, for example, that science has a "bourgeois and/or Eurocentric and/or masculinist world-view".

The anti-nuclear movement, often associated with the left, has been criticized for overstating the negative effects of nuclear power, and understating the environmental costs of non-nuclear sources that can be prevented through nuclear energy. Opposition to genetically modified organisms (GMOs) has also been associated with the left.

Right-wing

The origin of antiscience thinking may be traced back to the reaction of Romanticism to the Enlightenment, a movement often referred to as the Counter-Enlightenment. Romanticism emphasizes that intuition, passion, and organic links to nature are primal values and that rational thinking is merely a product of human life. Modern right-wing antiscience includes climate change denial, rejection of evolution, and misinformation about COVID-19 vaccines. While concentrated in areas of science that are seen as motivating government action, these attitudes are strong enough to make conservatives appreciate science less in general.

Characteristics of antiscience associated with the right include the appeal to conspiracy theories to explain why scientists believe what they believe, in an attempt to undermine the confidence or power usually associated to science (e.g., in global warming conspiracy theories). In modern times, it has been argued that right-wing politics carries an anti-science tendency. While some have suggested that this is innate to either rightists or their beliefs, others have argued it is a "quirk" of a historical and political context in which scientific findings happened to challenge or appeared to challenge the worldviews of rightists rather than leftists.

Religious

Main article: Relationship between religion and science

In this context, antiscience may be considered dependent on religious, moral, and cultural arguments. For this kind of religious antiscience philosophy, science is an anti-spiritual and materialistic force that undermines traditional values, ethnic identity, and accumulated historical wisdom in favor of reason and cosmopolitanism. In particular, the traditional and ethnic values emphasized are similar to those of white supremacist Christian Identity theology. Still, similar right-wing views have been developed by radically conservative sects of Islam, Judaism, Hinduism, and Buddhism. New religious movements such as the left-wing New Age and the far-right Falun Gong thinking also criticize the scientific worldview as favouring a reductionist, atheist, or materialist philosophy.

A frequent basis of antiscientific sentiment is religious theism with literal interpretations of sacred text. Here, scientific theories that conflict with divinely inspired knowledge are regarded as flawed. Over the centuries, religious institutions have been hesitant to embrace such ideas as heliocentrism and planetary motion because they contradict the dominant interpretation of various passages of scripture. More recently, the body of creation theologies known collectively as creationism, including the teleological theory of intelligent design, has been promoted by religious theists (primarily fundamentalists) in response to the process of evolution by natural selection. One of the more extreme creation theologies, young Earth creationism, also finds itself in conflict with research in cosmology, historical geology, and the origin of life. Young Earth creationism is predominantly exclusive to fundamentalist Protestant Christianity, though it is also present in Catholicism and Judaism, albeit to a lesser extent.

Studies suggest that a belief in spirituality rather than religion may better indicate an anti-science position.

To the extent that attempts to overcome antiscience sentiments have failed, some argue that a different approach to science advocacy is needed. One such approach says that it is important to develop a more accurate understanding of those who deny science (avoiding stereotyping them as backward and uneducated) and also to attempt outreach via those who share cultural values with target audiences, such as scientists who also hold religious beliefs.

Areas

There is a cult of ignorance in the United States, and there has always been. The strain of anti-intellectualism has been a constant thread winding its way through our political and cultural life, nurtured by the false notion that democracy means that "my ignorance is just as good as your knowledge".

Isaac Asimov, "A Cult of Ignorance", Newsweek, 21 January 1980

Historically, antiscience first arose as a reaction against scientific materialism. The 18th century Enlightenment had ushered in "the ideal of a unified system of all the sciences", but there were those fearful of this notion, who "felt that constrictions of reason and science, of a single all-embracing system... were in some way constricting, an obstacle to their vision of the world, chains on their imagination or feeling". Antiscience then is a rejection of "the scientific model [or paradigm]... with its strong implication that only that which was quantifiable, or at any rate, measurable... was real". In this sense, it comprises a "critical attack upon the total claim of the new scientific method to dominate the entire field of human knowledge". However, scientific positivism (logical positivism) does not deny the reality of non-measurable phenomena, only that those phenomena should not be adequate to scientific investigation. Moreover, positivism, as a philosophical basis for the scientific method, is not consensual or even dominant in the scientific community (see philosophy of science).

Recent developments and discussions around antiscience attitudes reveal how deeply intertwined these beliefs are with social, political, and psychological factors. A study published by Ohio State News on July 11, 2022, identified four primary bases that underpin antiscience beliefs: doubts about the credibility of scientific sources, identification with groups holding antiscience attitudes, conflicts between scientific messages and personal beliefs, and discrepancies between the presentation of scientific messages and individuals' thinking styles. These factors are exacerbated in the current political climate, where ideology significantly influences people's acceptance of science, particularly on topics that have become politically polarized, such as vaccines and climate change. The politicization of science poses a significant challenge to public health and safety, particularly in managing global crises like the COVID-19 pandemic.

The following quotes explore this aspect of four major areas of antiscience: philosophy, sociology, ecology and political.

Philosophy

Philosophical objections against science are often objections about the role of reductionism. For example, in the field of psychology, "both reductionists and antireductionists accept that... non-molecular explanations may not be improved, corrected or grounded in molecular ones". Further, "epistemological antireductionism holds that, given our finite mental capacities, we would not be able to grasp the ultimate physical explanation of many complex phenomena even if we knew the laws governing their ultimate constituents". Some see antiscience as "common...in academic settings...many people see that there are problems in demarcation between science, scientism, and pseudoscience resulting in an antiscience stance. Some argue that nothing can be known for sure".

Many philosophers are "divided as to whether reduction should be a central strategy for understanding the world". However, many agree that "there are, nevertheless, reasons why we want science to discover properties and explanations other than reductive physical ones". Such issues stem "from an antireductionist worry that there is no absolute conception of reality, that is, a characterization of reality such as... science claims to provide".

Sociology

Sociologist Thomas Gieryn refers to "some sociologists who might appear to be antiscience". Some "philosophers and antiscience types", he contends, may have presented "unreal images of science that threaten the believability of scientific knowledge", or appear to have gone "too far in their antiscience deconstructions". The question often lies in how much scientists conform to the standard ideal of "communalism, universalism, disinterestedness, originality, and... skepticism". "scientists don't always conform... scientists do get passionate about pet theories; they do rely on reputation in judging a scientist's work; they do pursue fame and gain via research". Thus, they may show inherent biases in their work. "[Many] scientists are not as rational and logical as the legend would have them, nor are they as illogical or irrational as some relativists might say".

Ecology and health sphere

Within the ecological and health spheres, Levins identifies a conflict "not between science and antiscience, but rather between different pathways for science and technology; between a commodified science-for-profit and a gentle science for humane goals; between the sciences of the smallest parts and the sciences of dynamic wholes... [he] offers proposals for a more holistic, integral approach to understanding and addressing environmental issues". These beliefs are also common within the scientific community, with for example, scientists being prominent in environmental campaigns warning of environmental dangers such as ozone depletion and the greenhouse effect. In the medical sphere, patients and practitioners may choose to reject science and adopt a pseudoscientific approach to health problems. This can be both a practical and a conceptual shift and has attracted strong criticism: "therapeutic touch, a healing technique based upon the laying-on of hands, has found wide acceptance in the nursing profession despite its lack of scientific plausibility. Its acceptance is indicative of a broad antiscientific trend in nursing".

Glazer also criticises the therapists and patients, "for abandoning the biological underpinnings of nursing and for misreading philosophy in the service of an antiscientific world-view". In contrast, Brian Martin criticized Gross and Levitt by saying that "[their] basic approach is to attack constructivists for not being positivists," and that science is "presented as a unitary object, usually identified with scientific knowledge. It is portrayed as neutral and objective. Second, science is claimed to be under attack by 'antiscience' which is composed essentially of ideologues who are threats to the neutrality and objectivity that are fundamental to science. Third, a highly selective attack is made on the arguments of 'antiscience'". Such people allegedly then "routinely equate critique of scientific knowledge with hostility to science, a jump that is logically unsupportable and empirically dubious". Having then "constructed two artificial entities, a unitary 'science' and a unitary 'academic left', each reduced to epistemological essences, Gross and Levitt proceed to attack. They pick out figures in each of several areas – science studies, postmodernism, feminism, environmentalism, AIDS activism – and criticise their critiques of science".

The writings of Young serve to illustrate more antiscientific views: "The strength of the antiscience movement and of alternative technology is that their advocates have managed to retain Utopian vision while still trying to create concrete instances of it". "The real social, ideological and economic forces shaping science...[have] been opposed to the point of suppression in many quarters. Most scientists hate it and label it 'antiscience'. But it is urgently needed, because it makes science self-conscious and hopefully self-critical and accountable with respect to the forces which shape research priorities, criteria, goals".

Genetically modified foods also bring about antiscience sentiment. The general public has recently become more aware of the dangers of a poor diet, as there have been numerous studies that show that the two are inextricably linked. Anti-science dictates that science is untrustworthy, because it is never complete and always being revised, which would be a probable cause for the fear that the general public has of genetically modified foods despite scientific reassurance that such foods are safe.

Antivaccinationists rely on whatever comes to hand presenting some of their arguments as if scientific; however, a strain of antiscience is part of their approach.

Political

Political scientist Tom Nichols, from Harvard Extension School and the U.S. Naval War College, points out that skepticism towards scientific expertise has increasingly become a symbol of political identity, especially within conservative circles. This skepticism is not just a result of misinformation but also reflects a broader cultural shift towards diminishing trust in experts and authoritative sources. This trend challenges the traditional neutrality of science, positioning scientific beliefs and facts within the contentious arena of political ideology.

The COVID-19 pandemic, for example, conflicting responses to public health measures and vaccine acceptance have highlighted the extent to which science has been politicized. Such polarization suggests that for some, rejecting scientific consensus or public health guidance serves as an expression of political allegiance or skepticism towards perceived authority figures.

This politicization of science complicates efforts to address public health crises and undermines the broader social contract that underpins scientific research and its application for the public good. The challenge lies not only in combating misinformation but also in bridging ideological divides that affect public trust in science. Strategies to counteract antiscience attitudes may need to encompass more than just presenting factual information; they might also need to engage with the underlying social and psychological factors that contribute to these attitudes, fostering dialogue that acknowledges different viewpoints and seeks common ground.

Antiscience media

Major antiscience media include portals Natural News, Global Revolution TV, TruthWiki.org, TheAntiMedia.org and GoodGopher. Antiscience views have also been supported on social media by organizations known to support fake news such as the web brigades.

Regulation of gene expression

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Regulation_of_gene_expression

Regulation of gene expression by a hormone receptor

Diagram showing at which stages in the DNA-mRNA-protein pathway expression can be controlled

Regulation of gene expression, or gene regulation, includes a wide range of mechanisms that are used by cells to increase or decrease the production of specific gene products (protein or RNA). Sophisticated programs of gene expression are widely observed in biology, for example to trigger developmental pathways, respond to environmental stimuli, or adapt to new food sources. Virtually any step of gene expression can be modulated, from transcriptional initiation, to RNA processing, and to the post-translational modification of a protein. Often, one gene regulator controls another, and so on, in a gene regulatory network.

Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed. Although as early as 1951, Barbara McClintock showed interaction between two genetic loci, Activator (Ac) and Dissociator (Ds), in the color formation of maize seeds, the first discovery of a gene regulation system is widely considered to be the identification in 1961 of the lac operon, discovered by François Jacob and Jacques Monod, in which some enzymes involved in lactose metabolism are expressed by E. coli only in the presence of lactose and absence of glucose.

In multicellular organisms, gene regulation drives cellular differentiation and morphogenesis in the embryo, leading to the creation of different cell types that possess different gene expression profiles from the same genome sequence. Although this does not explain how gene regulation originated, evolutionary biologists include it as a partial explanation of how evolution works at a molecular level, and it is central to the science of evolutionary developmental biology ("evo-devo").

Regulated stages of gene expression

Any step of gene expression may be modulated, from signaling to transcription to post-translational modification of a protein. The following is a list of stages where gene expression is regulated, where the most extensively utilized point is transcription initiation, the first stage in transcription:

• Signal transduction
• Chromatin, chromatin remodeling, chromatin domains
• Transcription
• Post-transcriptional modification
• RNA transport
• Translation
• mRNA degradation

Modification of DNA

Histone tails and their function in chromatin formation

In eukaryotes, the accessibility of large regions of DNA can depend on its chromatin structure, which can be altered as a result of histone modifications directed by DNA methylation, ncRNA, or DNA-binding protein. Hence these modifications may up or down regulate the expression of a gene. Some of these modifications that regulate gene expression are inheritable and are referred to as epigenetic regulation.

Structural

Transcription of DNA is dictated by its structure. In general, the density of its packing is indicative of the frequency of transcription. Octameric protein complexes called histones together with a segment of DNA wound around the eight histone proteins (together referred to as a nucleosome) are responsible for the amount of supercoiling of DNA, and these complexes can be temporarily modified by processes such as phosphorylation or more permanently modified by processes such as methylation. Such modifications are considered to be responsible for more or less permanent changes in gene expression levels.

Chemical

Methylation of DNA is a common method of gene silencing. DNA is typically methylated by methyltransferase enzymes on cytosine nucleotides in a CpG dinucleotide sequence (also called "CpG islands" when densely clustered). Analysis of the pattern of methylation in a given region of DNA (which can be a promoter) can be achieved through a method called bisulfite mapping. Methylated cytosine residues are unchanged by the treatment, whereas unmethylated ones are changed to uracil. The differences are analyzed by DNA sequencing or by methods developed to quantify SNPs, such as Pyrosequencing (Biotage) or MassArray (Sequenom), measuring the relative amounts of C/T at the CG dinucleotide. Abnormal methylation patterns are thought to be involved in oncogenesis.

Histone acetylation is also an important process in transcription. Histone acetyltransferase enzymes (HATs) such as CREB-binding protein also dissociate the DNA from the histone complex, allowing transcription to proceed. Often, DNA methylation and histone deacetylation work together in gene silencing. The combination of the two seems to be a signal for DNA to be packed more densely, lowering gene expression.

Regulation of transcription

Main article: Transcriptional regulation

1: RNA Polymerase, 2: Repressor, 3: Promoter, 4: Operator, 5: Lactose, 6: lacZ, 7: lacY, 8: lacA. Top: The gene is essentially turned off. There is no lactose to inhibit the repressor, so the repressor binds to the operator, which obstructs the RNA polymerase from binding to the promoter and making lactase. Bottom: The gene is turned on. Lactose is inhibiting the repressor, allowing the RNA polymerase to bind with the promoter, and express the genes, which synthesize lactase. Eventually, the lactase will digest all of the lactose, until there is none to bind to the repressor. The repressor will then bind to the operator, stopping the manufacture of lactase.

Regulation of transcription thus controls when transcription occurs and how much RNA is created. Transcription of a gene by RNA polymerase can be regulated by several mechanisms. Specificity factors alter the specificity of RNA polymerase for a given promoter or set of promoters, making it more or less likely to bind to them (i.e., sigma factors used in prokaryotic transcription). Repressors bind to the Operator, coding sequences on the DNA strand that are close to or overlapping the promoter region, impeding RNA polymerase's progress along the strand, thus impeding the expression of the gene. The image to the right demonstrates regulation by a repressor in the lac operon. General transcription factors position RNA polymerase at the start of a protein-coding sequence and then release the polymerase to transcribe the mRNA. Activators enhance the interaction between RNA polymerase and a particular promoter, encouraging the expression of the gene. Activators do this by increasing the attraction of RNA polymerase for the promoter, through interactions with subunits of the RNA polymerase or indirectly by changing the structure of the DNA. Enhancers are sites on the DNA helix that are bound by activators in order to loop the DNA bringing a specific promoter to the initiation complex. Enhancers are much more common in eukaryotes than prokaryotes, where only a few examples exist (to date). Silencers are regions of DNA sequences that, when bound by particular transcription factors, can silence expression of the gene.

Regulation by RNA

RNA can be an important regulator of gene activity, e.g. by microRNA (miRNA), antisense-RNA, or long non-coding RNA (lncRNA). LncRNAs differ from mRNAs in the sense that they have specified subcellular locations and functions. They were first discovered to be located in the nucleus and chromatin, and the localizations and functions are highly diverse now. Some still reside in chromatin where they interact with proteins. While this lncRNA ultimately affects gene expression in neuronal disorders such as Parkinson, Huntington, and Alzheimer disease, others, such as, PNCTR(pyrimidine-rich non-coding transcriptors), play a role in lung cancer. Given their role in disease, lncRNAs are potential biomarkers and may be useful targets for drugs or gene therapy, although there are no approved drugs that target lncRNAs yet. The number of lncRNAs in the human genome remains poorly defined, but some estimates range from 16,000 to 100,000 lnc genes.

Epigenetic gene regulation

Overview of Epigenetic mechanisms.

Epigenetics refers to the modification of genes that is not changing the DNA or RNA sequence. Epigenetic modifications are also a key factor in influencing gene expression. They occur on genomic DNA and histones and their chemical modifications regulate gene expression in a more efficient manner. There are several modifications of DNA (usually methylation) and more than 100 modifications of RNA in mammalian cells." Those modifications result in altered protein binding to DNA and a change in RNA stability and translation efficiency.

Special cases in human biology and disease

Regulation of transcription in cancer

Main article: Regulation of transcription in cancer

In vertebrates, the majority of gene promoters contain a CpG island with numerous CpG sites. When many of a gene's promoter CpG sites are methylated the gene becomes silenced. Colorectal cancers typically have 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, transcriptional silencing may be of more importance than mutation in causing progression to cancer. For example, in colorectal cancers about 600 to 800 genes are transcriptionally silenced by CpG island methylation (see regulation of transcription in cancer). Transcriptional repression in cancer can also occur by other epigenetic mechanisms, such as altered expression of microRNAs. In breast cancer, transcriptional repression of BRCA1 may occur more frequently by over-expressed microRNA-182 than by hypermethylation of the BRCA1 promoter (see Low expression of BRCA1 in breast and ovarian cancers).

Regulation of transcription in addiction

One of the cardinal features of addiction is its persistence. The persistent behavioral changes appear to be due to long-lasting changes, resulting from epigenetic alterations affecting gene expression, within particular regions of the brain. Drugs of abuse cause three types of epigenetic alteration in the brain. These are (1) histone acetylations and histone methylations, (2) DNA methylation at CpG sites, and (3) epigenetic downregulation or upregulation of microRNAs. (See Epigenetics of cocaine addiction for some details.)

Chronic nicotine intake in mice alters brain cell epigenetic control of gene expression through acetylation of histones. This increases expression in the brain of the protein FosB, important in addiction. Cigarette addiction was also studied in about 16,000 humans, including never smokers, current smokers, and those who had quit smoking for up to 30 years. In blood cells, more than 18,000 CpG sites (of the roughly 450,000 analyzed CpG sites in the genome) had frequently altered methylation among current smokers. These CpG sites occurred in over 7,000 genes, or roughly a third of known human genes. The majority of the differentially methylated CpG sites returned to the level of never-smokers within five years of smoking cessation. However, 2,568 CpGs among 942 genes remained differentially methylated in former versus never smokers. Such remaining epigenetic changes can be viewed as "molecular scars" that may affect gene expression.

In rodent models, drugs of abuse, including cocaine, methamphetamin,  alcohol and tobacco smoke products, all cause DNA damage in the brain. During repair of DNA damages some individual repair events can alter the methylation of DNA and/or the acetylations or methylations of histones at the sites of damage, and thus can contribute to leaving an epigenetic scar on chromatin.

Such epigenetic scars likely contribute to the persistent epigenetic changes found in addiction.

Regulation of transcription in learning and memory

DNA methylation is the addition of a methyl group to the DNA that happens at cytosine. The image shows a cytosine single ring base and a methyl group added on to the 5 carbon. In mammals, DNA methylation occurs almost exclusively at a cytosine that is followed by a guanine.

In mammals, methylation of cytosine (see Figure) in DNA is a major regulatory mediator. Methylated cytosines primarily occur in dinucleotide sequences where cytosine is followed by a guanine, a CpG site. The total number of CpG sites in the human genome is approximately 28 million. and generally about 70% of all CpG sites have a methylated cytosine.

The identified areas of the human brain are involved in memory formation.

In a rat, a painful learning experience, contextual fear conditioning, can result in a life-long fearful memory after a single training event. Cytosine methylation is altered in the promoter regions of about 9.17% of all genes in the hippocampus neuron DNA of a rat that has been subjected to a brief fear conditioning experience. The hippocampus is where new memories are initially stored.

Methylation of CpGs in a promoter region of a gene represses transcription while methylation of CpGs in the body of a gene increases expression. TET enzymes play a central role in demethylation of methylated cytosines. Demethylation of CpGs in a gene promoter by TET enzyme activity increases transcription of the gene.

When contextual fear conditioning is applied to a rat, more than 5,000 differentially methylated regions (DMRs) (of 500 nucleotides each) occur in the rat hippocampus neural genome both one hour and 24 hours after the conditioning in the hippocampus. This causes about 500 genes to be up-regulated (often due to demethylation of CpG sites in a promoter region) and about 1,000 genes to be down-regulated (often due to newly formed 5-methylcytosine at CpG sites in a promoter region). The pattern of induced and repressed genes within neurons appears to provide a molecular basis for forming the first transient memory of this training event in the hippocampus of the rat brain.

Post-transcriptional regulation

Main article: Post-transcriptional regulation

After the DNA is transcribed and mRNA is formed, there must be some sort of regulation on how much the mRNA is translated into proteins. Cells do this by modulating the capping, splicing, addition of a Poly(A) Tail, the sequence-specific nuclear export rates, and, in several contexts, sequestration of the RNA transcript. These processes occur in eukaryotes but not in prokaryotes. This modulation is a result of a protein or transcript that, in turn, is regulated and may have an affinity for certain sequences.

Three prime untranslated regions and microRNAs

Main article: Three prime untranslated region

Main article: MicroRNA

Three prime untranslated regions (3'-UTRs) of messenger RNAs (mRNAs) often contain regulatory sequences that post-transcriptionally influence gene expression. Such 3'-UTRs often contain both binding sites for microRNAs (miRNAs) as well as for regulatory proteins. By binding to specific sites within the 3'-UTR, miRNAs can decrease gene expression of various mRNAs by either inhibiting translation or directly causing degradation of the transcript. The 3'-UTR also may have silencer regions that bind repressor proteins that inhibit the expression of a mRNA.

The 3'-UTR often contains miRNA response elements (MREs). MREs are sequences to which miRNAs bind. These are prevalent motifs within 3'-UTRs. Among all regulatory motifs within the 3'-UTRs (e.g. including silencer regions), MREs make up about half of the motifs.

As of 2014, the miRBase web site, an archive of miRNA sequences and annotations, listed 28,645 entries in 233 biologic species. Of these, 1,881 miRNAs were in annotated human miRNA loci. miRNAs were predicted to have an average of about four hundred target mRNAs (affecting expression of several hundred genes). Freidman et al. estimate that >45,000 miRNA target sites within human mRNA 3'-UTRs are conserved above background levels, and >60% of human protein-coding genes have been under selective pressure to maintain pairing to miRNAs.

Direct experiments show that a single miRNA can reduce the stability of hundreds of unique mRNAs. Other experiments show that a single miRNA may repress the production of hundreds of proteins, but that this repression often is relatively mild (less than 2-fold).

The effects of miRNA dysregulation of gene expression seem to be important in cancer. For instance, in gastrointestinal cancers, a 2015 paper identified nine miRNAs as epigenetically altered and effective in down-regulating DNA repair enzymes.

The effects of miRNA dysregulation of gene expression also seem to be important in neuropsychiatric disorders, such as schizophrenia, bipolar disorder, major depressive disorder, Parkinson's disease, Alzheimer's disease and autism spectrum disorders.

Regulation of translation

Main article: Translational regulation

The translation of mRNA can also be controlled by a number of mechanisms, mostly at the level of initiation. Recruitment of the small ribosomal subunit can indeed be modulated by mRNA secondary structure, antisense RNA binding, or protein binding. In both prokaryotes and eukaryotes, a large number of RNA binding proteins exist, which often are directed to their target sequence by the secondary structure of the transcript, which may change depending on certain conditions, such as temperature or presence of a ligand (aptamer). Some transcripts act as ribozymes and self-regulate their expression.

Examples of gene regulation

• Enzyme induction is a process in which a molecule (e.g., a drug) induces (i.e., initiates or enhances) the expression of an enzyme.
• The induction of heat shock proteins in the fruit fly Drosophila melanogaster.
• The Lac operon is an interesting example of how gene expression can be regulated.
• Viruses, despite having only a few genes, possess mechanisms to regulate their gene expression, typically into an early and late phase, using collinear systems regulated by anti-terminators (lambda phage) or splicing modulators (HIV).
• Gal4 is a transcriptional activator that controls the expression of GAL1, GAL7, and GAL10 (all of which code for the metabolic of galactose in yeast). The GAL4/UAS system has been used in a variety of organisms across various phyla to study gene expression.

Developmental biology

Main article: Evolutionary developmental biology

A large number of studied regulatory systems come from developmental biology. Examples include:

• The colinearity of the Hox gene cluster with their nested antero-posterior patterning
• Pattern generation of the hand (digits - interdigits): the gradient of sonic hedgehog (secreted inducing factor) from the zone of polarizing activity in the limb, which creates a gradient of active Gli3, which activates Gremlin, which inhibits BMPs also secreted in the limb, results in the formation of an alternating pattern of activity as a result of this reaction–diffusion system.
• Somitogenesis is the creation of segments (somites) from a uniform tissue (Pre-somitic Mesoderm). They are formed sequentially from anterior to posterior. This is achieved in amniotes possibly by means of two opposing gradients, Retinoic acid in the anterior (wavefront) and Wnt and Fgf in the posterior, coupled to an oscillating pattern (segmentation clock) composed of FGF + Notch and Wnt in antiphase.
• Sex determination in the soma of a Drosophila requires the sensing of the ratio of autosomal genes to sex chromosome-encoded genes, which results in the production of sexless splicing factor in females, resulting in the female isoform of doublesex.

Circuitry

Main article: Gene regulatory network

Up-regulation and down-regulation

Up-regulation is a process which occurs within a cell triggered by a signal (originating internal or external to the cell), which results in increased expression of one or more genes and as a result the proteins encoded by those genes. Conversely, down-regulation is a process resulting in decreased gene and corresponding protein expression.

• Up-regulation occurs, for example, when a cell is deficient in some kind of receptor. In this case, more receptor protein is synthesized and transported to the membrane of the cell and, thus, the sensitivity of the cell is brought back to normal, reestablishing homeostasis.
• Down-regulation occurs, for example, when a cell is overstimulated by a neurotransmitter, hormone, or drug for a prolonged period of time, and the expression of the receptor protein is decreased in order to protect the cell (see also tachyphylaxis).

Inducible vs. repressible systems

Gene regulation works using operators and repressors in bacteria.

Gene Regulation can be summarized by the response of the respective system:

• Inducible systems - An inducible system is off unless there is the presence of some molecule (called an inducer) that allows for gene expression. The molecule is said to "induce expression". The manner by which this happens is dependent on the control mechanisms as well as differences between prokaryotic and eukaryotic cells.
• Repressible systems - A repressible system is on except in the presence of some molecule (called a corepressor) that suppresses gene expression. The molecule is said to "repress expression". The manner by which this happens is dependent on the control mechanisms as well as differences between prokaryotic and eukaryotic cells.

The GAL4/UAS system is an example of both an inducible and repressible system. Gal4 binds an upstream activation sequence (UAS) to activate the transcription of the GAL1/GAL7/GAL10 cassette. On the other hand, a MIG1 response to the presence of glucose can inhibit GAL4 and therefore stop the expression of the GAL1/GAL7/GAL10 cassette.

Theoretical circuits

• Repressor/Inducer: an activation of a sensor results in the change of expression of a gene
• negative feedback: the gene product downregulates its own production directly or indirectly, which can result in
  • keeping transcript levels constant/proportional to a factor
  • inhibition of run-away reactions when coupled with a positive feedback loop
  • creating an oscillator by taking advantage in the time delay of transcription and translation, given that the mRNA and protein half-life is shorter
• positive feedback: the gene product upregulates its own production directly or indirectly, which can result in
  • signal amplification
  • bistable switches when two genes inhibit each other and both have positive feedback
  • pattern generation

Study methods

Schematic karyogram of a human, showing an overview of the human genome on G banding, which is a method that includes Giemsa staining, wherein the lighter staining regions are generally more transcriptionally active, whereas darker regions are more inactive.

Further information: Karyotype

For DNA and RNA methods, see nucleic acid methods.

For protein methods, see protein methods.

In general, most experiments investigating differential expression used whole cell extracts of RNA, called steady-state levels, to determine which genes changed and by how much. These are, however, not informative of where the regulation has occurred and may mask conflicting regulatory processes (see post-transcriptional regulation), but it is still the most commonly analysed (quantitative PCR and DNA microarray).

When studying gene expression, there are several methods to look at the various stages. In eukaryotes these include:

• The local chromatin environment of the region can be determined by ChIP-chip analysis by pulling down RNA Polymerase II, Histone 3 modifications, Trithorax-group protein, Polycomb-group protein, or any other DNA-binding element to which a good antibody is available.
• Epistatic interactions can be investigated by synthetic genetic array analysis
• Due to post-transcriptional regulation, transcription rates and total RNA levels differ significantly. To measure the transcription rates nuclear run-on assays can be done and newer high-throughput methods are being developed, using thiol labelling instead of radioactivity.
• Only 5% of the RNA polymerised in the nucleus exits, and not only introns, abortive products, and non-sense transcripts are degradated. Therefore, the differences in nuclear and cytoplasmic levels can be seen by separating the two fractions by gentle lysis.
• Alternative splicing can be analysed with a splicing array or with a tiling array (see DNA microarray).
• All in vivo RNA is complexed as RNPs. The quantity of transcripts bound to specific protein can be also analysed by RIP-Chip. For example, DCP2 will give an indication of sequestered protein; ribosome-bound gives and indication of transcripts active in transcription (although a more dated method, called polysome fractionation, is still popular in some labs).
• Protein levels can be analysed by Mass spectrometry, which can be compared only to quantitative PCR data, as microarray data is relative and not absolute.
• RNA and protein degradation rates are measured by means of transcription inhibitors (actinomycin D or α-Amanitin) or translation inhibitors (Cycloheximide), respectively.