A somatic epitype is a non-heritable epigenetic alteration in a gene. It is similar to conventional epigenetics in that it does not involve changes in the DNA primary sequence. Physically, the somatic epitype corresponds to changes in DNA methylation, oxidative damage (replacement of GTP with oxo-8-dGTP), or changes in DNA-chromatin structure that are not reversed by normal cellular or nuclear repair mechanisms. Somatic epitypes alter gene expression levels without altering the amino acid sequence of the expressed protein. Current research suggests that somatic epitypes can be altered both before and after birth, and this alteration can be in response to exposure to heavy metals (such as lead), differences in maternal care, or nutritional or behavioral stress. There is no indication that somatic epitypes are heritable in a conventional epigenetic fashion. Some research suggests that methylation levels (and gene expression) can be reversed for some somatic epitypes by alterations in environmental factors such as diet.
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In biology, epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence. The Greek prefix epi- in epigenetics implies features that are "on top of" or "in addition to" the traditional genetic basis for inheritance. Epigenetics most often involves changes that affect gene activity and expression, but the term can also be used to describe any heritable phenotypic change. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors, or be part of normal development. The standard definition of epigenetics requires these alterations to be heritable in the progeny of either cells or organisms.
Cellular differentiation is the process in which a cell changes from one cell type to another. Usually, the cell changes to a more specialized type. Differentiation occurs numerous times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. Although metabolic composition does get altered quite dramatically where stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. Thus, different cells can have very different physical characteristics despite having the same genome.
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. 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.
A neoplasm is a type of abnormal and excessive growth, called neoplasia, of tissue. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor.
Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cells are transformed into cancer cells. The process is characterized by changes at the cellular, genetic, and epigenetic levels and abnormal cell division. Cell division is a physiological process that occurs in almost all tissues and under a variety of circumstances. Normally the balance between proliferation and programmed cell death, in the form of apoptosis, is maintained to ensure the integrity of tissues and organs. According to the prevailing accepted theory of carcinogenesis, the somatic mutation theory, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by disrupting the programming regulating the processes, upsetting the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. Only certain mutations lead to cancer whereas the majority of mutations do not.
In epigenetics, a paramutation is an interaction between two alleles at a single locus, whereby one allele induces a heritable change in the other allele. The change may be in the pattern of DNA methylation or histone modifications. The allele inducing the change is said to be paramutagenic, while the allele that has been epigenetically altered is termed paramutable. A paramutable allele may have altered levels of gene expression, which may continue in offspring which inherit that allele, even though the paramutagenic allele may no longer be present. Through proper breeding, paramutation can result in siblings that have the same genetic sequence, but with drastically different phenotypes.
In biology, reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development or in cell culture. Such control is also often associated with alternative covalent modifications of histones.
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It is a characteristic that would not be observed naturally in a specimen. The term mutant is also applied to a virus with an alteration in its nucleotide sequence whose genome is RNA, rather than DNA. In multicellular eukaryotes, a DNA sequence may be altered in an individual somatic cell that then gives rise to a mutant somatic cell lineage as happens in cancer progression. Also in eukaryotes, alteration of a mitochondrial or plastid DNA sequence may give rise to a mutant lineage that is inherited separately from mutant genotypes in the nuclear genome. The natural occurrence of genetic mutations is integral to the process of evolution. The study of mutants is an integral part of biology; by understanding the effect that a mutation in a gene has, it is possible to establish the normal function of that gene.
Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome. The field is analogous to genomics and proteomics, which are the study of the genome and proteome of a cell. Epigenetic modifications are reversible modifications on a cell's DNA or histones that affect gene expression without altering the DNA sequence. Epigenomic maintenance is a continuous process and plays an important role in stability of eukaryotic genomes by taking part in crucial biological mechanisms like DNA repair. Plant flavones are said to be inhibiting epigenomic marks that cause cancers. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis. The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays.
Nutriepigenomics is the study of food nutrients and their effects on human health through epigenetic modifications. There is now considerable evidence that nutritional imbalances during gestation and lactation are linked to non-communicable diseases, such as obesity, cardiovascular disease, diabetes, hypertension, and cancer. If metabolic disturbances occur during critical time windows of development, the resulting epigenetic alterations can lead to permanent changes in tissue and organ structure or function and predispose individuals to disease.
Transgenerational epigenetic inheritance is the transmission of epigenetic markers from one organism to the next that affects the traits of offspring without altering the primary structure of DNA —in other words, epigenetically. The less precise term "epigenetic inheritance" may cover both cell–cell and organism–organism information transfer. Although these two levels of epigenetic inheritance are equivalent in unicellular organisms, they may have distinct mechanisms and evolutionary distinctions in multicellular organisms.
Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development. They may be just as important, or even more important, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing than by mutations. As Vogelstein et al. point out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66 hitchhiker or passenger mutations. However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa. Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy. In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as silencing of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. Several medications which have epigenetic impact are now used in several of these diseases.
Behavioral epigenetics is the field of study examining the role of epigenetics in shaping animal behaviour. It seeks to explain how nurture shapes nature, where nature refers to biological heredity and nurture refers to virtually everything that occurs during the life-span. Behavioral epigenetics attempts to provide a framework for understanding how the expression of genes is influenced by experiences and the environment to produce individual differences in behaviour, cognition, personality, and mental health.
The epigenetics of schizophrenia is the study of how the inherited epigenetic changes are regulated and modified by the environment and external factors, and how these changes shape and influence the onset and development of, and vulnerability to, schizophrenia. Epigenetics also studies how these genetic modifications can be passed on to future generations. Schizophrenia is a debilitating and often misunderstood disorder that affects up to 1% of the world's population. While schizophrenia is a heavily-studied disorder, it has remained largely impervious to scientific understanding, so epigenetics offers a new avenue for research, understanding, and treatment.
Epigenetic theories of homosexuality concern the studies of changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence, and their role in the development of homosexuality. Epigenetics examines the set of chemical reactions that switch parts of the genome on and off at strategic times and locations in the organism's life cycle. However, epigenetic theories tangle a multiplicity of initiating causes and of resulting final effects and will never lead to a single cause or a single result. Hence, any interpretation of such theories may not focus just one isolated reason of a multiplicity of causes or of effects.
Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. Epigenetic therapy offers a potential way to influence those pathways directly.
Epigenetics of physical exercise is the study of epigenetic modifications resulting from physical exercise to the genome of cells. Epigenetic modifications are heritable alterations that are not due to changes in the sequence of nucleotides. Epigenetic modifications, such as histone modifications and DNA methylation, alter the accessibility to DNA and change chromatin structure, thereby regulating patterns of gene expression. Methylated histones can act as binding sites for certain transcription factors due to their bromodomains and chromodomains. Methylated histones can also prevent the binding of transcription factors by hiding the transcription factor's recognition site, which is usually found on the major groove of DNA. The methyl groups bound to the cytosine residues lie in the major groove of DNA, the same region most transcription factors use to read a DNA sequence. A common epigenetic tag found in DNA is the covalent attachment of a methyl group to the C5 position of the cytosine found in CpG dinucleotide sequences. CpG methylation is an important mechanism of transcriptional silencing. Methylation of CpG islands is shown to reduce gene expression by the formation of tightly condensed heterochromatin that is transcriptionally inactive. CpG sites in a gene are most commonly found in the promoter regions of a gene while also being present in non promoter regions. The CpG sites in non promoter regions tend to be constitutively methylated, causing transcription machinery to ignore them as possible promoters. The CpG site near promoter regions are mostly left unmethylated until a cell decides to methylate them and repress transcription. Methylation of CpGs in promoter regions result in the transcriptional silencing of a gene. Environmental factors including physical exercise have been shown to have a beneficial influence on epigenetic modifications.
Epigenetics is the study of changes in gene expression that occur via mechanisms such as DNA methylation, histone acetylation, and microRNA modification. When these epigenetics changes are heritable, they can influence evolution. Current research indicates that epigenetics has influenced evolution in a number of organisms, including plants and animals.
Transgenerational stress inheritance is the transmission of adverse effects of stress-exposure in parents to their offspring through epigenetic mechanisms.
Transgenerational epigenetic inheritance in plants involves mechanisms for the passing of epigenetic marks from parent to offspring that differ from those reported in animals. There are several kinds of epigenetic markers, but they all provide a mechanism to facilitate greater phenotypic plasticity by influencing the expression of genes without altering the DNA code. These modifications represent responses to environmental input and are reversible changes to gene expression patterns that can be passed down through generations. In plants, transgenerational epigenetic inheritance could potentially represent an evolutionary adaptation for sessile organisms to quickly adapt to their changing environment.