This article is part of the series on: Gene expression a Molecular biology topic (portal)

Introduction to Genetics

General flow: DNA > RNA > Protein

special transfers (RNA > RNA, RNA > DNA, Protein > Protein)

Genetic code

Transcription

Transcription (Transcription factors, RNA Polymerase,promoter)

post-transcriptional modification (hnRNA,Splicing)

Translation

Translation (Ribosome,tRNA)

post-translational modification (functional groups, peptides, structural changes)

gene regulation

epigenetic regulation (Hox genes, Genomic imprinting)

transcriptional regulation

post-transcriptional regulation (sequestration, alternative splicing,miRNA)

post-translational regulation (reversible,irrevesible)

In biology, the term epigenetics refers to changes in gene expression that are stable between cell divisions, and sometimes between generations, but do not involve changes in the underlying DNA sequence of the organism. Foundations of modern biology There are five unifying principles History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known ^[1] Basically, it is a term used to describe the idea that environmental factors can cause an organism's genes to behave (or "express themselves") differently, even though the genes themselves don't change. ^[2] The molecular basis of epigenetics involves modifications to DNA and the chromatin proteins that associate with it. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known Chromatin is the complex basis of DNA and protein that makes up Chromosomes It is found inside the nuclei of eukaryotic cells, and within the Epigenetics is a fundamental part of eukaryotic biology, and is perhaps most elegantly illustrated in the process of cellular differentiation, which allows cells to stably maintain different characteristics despite containing the same genomic material. Animals Plants fungi, and Protists are eukaryotes (juːˈkærɪɒt or -oʊt Organisms whose cells are organized into complex MOrphogenesis is an EP by Industrial Black metal band.And Oceans. Epigenetic states are inherited when cells divide, and although most of these states are considered dynamic over the course of development in multicellular organisms, some epigenetic features show transgenerational inheritance and are inherited from one generation to the next. ^[3]

Specific epigenetic processes include paramutation, bookmarking, imprinting, gene silencing, X chromosome inactivation, position effect, reprogramming, transvection, maternal effects, the progress of carcinogenesis, many effects of teratogens, regulation of histone modifications and heterochromatin, and technical limitations affecting parthenogenesis and cloning. In Epigenetics, paramutation is an interaction between two Alleles of a single locus, resulting in a heritable change of one allele that is induced by the In Genetics and Epigenetics, bookmarking is a biological phenomenon believed to function as an epigenetic mechanism for transmitting Cellular memory of Genomic imprinting is a genetic phenomenon by which certain Genes are expressed in a Parent -of-origin-specific manner Gene silencing is a general term describing Epigenetic processes of Gene regulation. X-inactivation (also called lyonization) is a process by which one of the two copies of the X chromosome present in Female Mammals is inactivated Position effect is the effect on the expression of a Gene when its location in a Chromosome is changed often by translocation. Reprogramming refers to erasure and remodeling of epigenetic marks such as DNA methylation, during mammalian development Transvection is an Epigenetic phenomenon that results from an interaction between an Allele on one Chromosome and the corresponding allele on the homologous A maternal effect, in genetics is the phenomenon where the Genotype of a mother is expressed in the Phenotype of its offspring unaltered by paternal genetic Carcinogenesis (meaning literally the creation of Cancer) is the process by which normal cells are transformed into cancer cells Teratology stems from the Greek ( Genitive) meaning monster, or marvel and, meaning word, speech. In Biology, histones are the chief Protein components of Chromatin. Heterochromatin is a tightly packed form of DNA Its major characteristic is that transcription is limited Parthenogenesis (from the Greek παρθένος parthenos, "virgin" + γένεσις genesis, "creation" is an asexual form Cloning in Biology is the process of producing populations of genetically-identical individuals that occurs in nature when organisms such as Bacteria, Insects

Epigenetic research uses a wide range of molecular biologic techniques to further our understanding of epigenetic phenomena, including chromatin immunoprecipitation (together with its large-scale variants ChIP-on-chip and ChIP-seq), fluorescent in situ hybridization, methylation-sensitive restriction enzymes, DNA adenine methyltransferase identification (DamID) and bisulfite sequencing. ChIP-on-chip (also known as ChIP-chip) is a technique that combines Chromatin immunoprecipitation ( "ChIP") with microarray technology FISH ( Fluorescent In situ hybridization) is a cytogenetic technique that can be used to detect and localize the presence or absence A restriction enzyme (or restriction Endonuclease) is an Enzyme that cuts double-stranded DNA at specific recognition Nucleotide DamID (DNA adenine methyltransferase identification is a Molecular biology protocol used to map the binding sites of DNA -binding Proteins in Eukaryotes Bisulfite sequencing is the use of Bisulfite treatment of DNA to determine its pattern of methylation Furthermore, the use of bioinformatic methods is playing an increasing role (computational epigenetics). Bioinformatics is the application of information technology to the field of molecular biology Computational epigenetics uses Bioinformatic methods to complement experimental research in Epigenetics.

Etymology and definitions

The word "epigenetics" has been associated with many different definitions, and much of the confusion surrounding the use of the word "epigenetics" relates to the fact that it was originally defined to explain phenomena without knowing their molecular basis and with time became narrowly linked to certain phenomena as their molecular basis was discovered. ^[4]

The word "epigenetics" (as in "epigenetic landscape") was coined by C. H. Waddington in 1942 as a portmanteau of the words "genetics" and "epigenesis". Epigenetic landscape is a Metaphor for biological development. Conrad Hal Waddington FRS FRSE (1905&ndash1975 was a developmental Biologist, paleontologist, Geneticist, Embryologist Genetics (from Ancient Greek grc-Latn genetikos, “genitive” and that from grc-Latn genesis, “origin” a discipline of Biology, is In Biology, epigenesis has at least two distinct meanings the unfolding development in an organism and in particular the development of a plant ^[5] Epigenesis is an older word used to describe the differentiation of cells from a totipotent state in embryonic development (used in contrast to "preformationism"). Totipotency is the ability of a single cell to divide and produce all the differentiated cells in an Organism, including extraembryonic tissues At the time Waddington first used the term "epigenetics," the physical nature of genes and their role in heredity was not known. Epigenetics was Waddington's model of how genes within a multicellular organism interact with their surroundings to produce a phenotype. A phenotype is any observable characteristic of an Organism, such as its morphology, Development, biochemical or physiological properties Because all cells within an organism inherit the same DNA sequences, cellular differentiation processes crucial for epigenesis rely strongly on epigenetic rather than genetic inheritance. In Developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized Cell type. Robin Holliday defined epigenetics as "the study of the mechanisms of temporal and spatial control of gene activity during the development of complex organisms. Robin Holliday proposed a mechanism of DNA-strand exchange that attempted to explain gene-conversion events that occur during meiosis in fungi "^[6] Thus, the word "epigenetic" can be used to describe any aspect other than DNA sequence that influences the development of an organism.

Another usage of the word "epigenetics" was employed by the psychologist Erik Erikson, who developed an "epigenetic theory of human development," which focuses on psycho-social crises. Erik Homburger Erikson ( June 15, 1902 – May 12, 1994) was born in Frankfurt to Danish parents but later obtained

The modern usage of the word "epigenetic" is usually more narrow, referring to heritable traits (over rounds of cell division and sometimes transgenerationally) that do not involve changes to the underlying DNA sequence. ^[7] The Greek prefix "epi-" in the word "epigenetics" implies features that are "on top of" or "in addition to" genetics, and the current usage of the word reflects this—epigenetic traits exist on top of or in addition to the traditional molecular basis for inheritance.

The similarity of the word to "genetics" has generated many parallel usages. The "epigenome" is a parallel to the word "genome," and refers to the overall epigenetic state of a cell. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby The phrase "genetic code" has also been adapted—the "epigenetic code" has been used to describe the set of epigenetic features that create different phenotypes in different cells. The genetic code is the set of rules by which information encoded in genetic material ( DNA or RNA sequences is translated into Proteins The epigenetic code is hypothesized to be a defining code in every Eukaryotic cell consisting of the specific Epigenetic modification in each cell Taken to its extreme, the "epigenetic code" could represent the total state of the cell, with the position of each molecule accounted for; more typically, the term is used in reference to systematic efforts to measure specific, relevant forms of epigenetic information such as the histone code or DNA methylation patterns. The Histone Code is hypothesized to be a code consisting of covalent Histone tail modifications DNA methylation is a type of chemical modification of DNA that can be inherited and subsequently removed without changing the original DNA sequence

Mechanisms

Several types of epigenetic inheritance systems may play a role in what has become known as cell memory:^[8]

DNA methylation and chromatin remodeling

DNA associates with histone proteins to form chromatin.

Because the phenotype of a cell or individual is affected by which of its genes are transcribed, heritable transcription states can give rise to epigenetic effects. A phenotype is any observable characteristic of an Organism, such as its morphology, Development, biochemical or physiological properties Transcription is the synthesis of RNA under the direction of DNA There are several layers of regulation of gene expression, one of which is remodeling of chromatin, the complex of DNA and the histone proteins with which it associates. Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such In Biology, histones are the chief Protein components of Chromatin. Chromatin remodeling is initiated by one of two things:

1. posttranslational modification of the amino acids that make up histone proteins,
2. or the addition of methyl groups to the DNA, at CpG sites, to convert cytosine to 5-methylcytosine. Posttranslational modification (PTM is the chemical modification of a Protein after its translation. CpG sites are regions of DNA where a Cytosine Nucleotide occurs next to a Guanine nucleotide in the linear sequence of bases 5-Methylcytosine is a methylated form of Cytosine in which a Methyl group is attached to carbon 5 altering its structure without altering its base-pairing

Whereas DNA is not completely stripped of nucleosomes during replication, it is possible that the remaining modified histones may act as templates, initiating identical modification of surrounding new histones after deposition. Nucleosomes form the fundamental repeating units of eukaryotic Chromatin, which is used to pack the large eukaryotic genomes into the nucleus while still ensuring DNA methylation has a more clear method of propagation through the preferential methylation of hemimethylated symmetric sites by enzymes like Dnmt 1.

Although modifications occur throughout the histone sequence, the unstructured termini of histones (called histone tails) are particularly highly modified. These modifications include acetylation, methylation and ubiquitylation. Acetylation (or in IUPAC nomenclature ethanoylation) describes a reaction that introduces an Acetyl Functional group into an Organic compound Methylation is a term used in the chemical sciences to denote the attachment or substitution of a methyl group on various substrates. Ubiquitin is a highly-conserved regulatory Protein that is ''ubiquitously'' expressed in Eukaryotes. Acetylation is the most highly studied of these modifications. For example, acetylation of the K14 and K9 lysines of the tail of histone H3 by histone acetyltransferase enzymes (HATs) is generally correlated with transcriptional competence. Lysine (abbreviated as Lys or K) is an α- Amino acid with the Chemical formula HO2CCH(NH2(CH24NH2

One mode of thinking is that this tendency of acetylation to be associated with "active" transcription is biophysical in nature. Because lysine normally has a positive charge on the nitrogen at its end, lysine can bind the negatively charged phosphates of the DNA backbone and prevent them from repelling each other. The acetylation event converts the positively charged amine group on the side chain into a neutral amide linkage. This removes the positive charge causing the DNA to repel itself. When this occurs, complexes like SWI/SNF and other transcriptional factors can bind to the DNA, thus opening it up and exposing it to enzymes like RNA polymerase so transcription of the gene can occur. RNA polymerase ( RNAP or RNApol) is an Enzyme that produces RNA.

In addition, the positively charged tails of histone proteins from one nucleosome may interact with the histone proteins on a neighboring nucleosome, causing them to pack closely. Lysine acetylation may interfere with these interactions, causing the chromatin structure to open up.

Lysine acetylation may also act as a beacon to recruit other activating chromatin modifying enzymes (and basal transcription machinery as well). Indeed, the bromodomain—a protein segment (domain) that specifically binds acetyl-lysine—is found in many enzymes that help activate transcription including the SWI/SNF complex (on the protein polybromo). It may be that acetylation acts in this and the previous way to aid in transcriptional activation.

The idea that modifications act as docking modules for related factors is borne out by histone methylation as well. Methylation of lysine 9 of histone H3 has long been associated with constitutively transcriptionally silent chromatin (constitutive heterochromatin). Heterochromatin is a tightly packed form of DNA Its major characteristic is that transcription is limited It has been determined that a chromodomain (a domain that specifically binds methyl-lysine) in the transcriptionally repressive protein HP1 recruits HP1 to K9 methylated regions. The family of Heterochromatin Protein 1 (HP1 ("Chromobox Homolog" CBX are highly conserved adapter molecules which have important functions in the Cell nucleus One example that seems to refute the biophysical model for acetylation is that tri-methylation of histone H3 at lysine 4 is strongly associated with (and required for full) transcriptional activation. Tri-methylation in this case would introduce a fixed positive charge on the tail.

It should be emphasized that differing histone modifications are likely to function in differing ways; acetylation at one position is likely to function differently than acetylation at another position. Also, multiple modifications may occur at the same time, and these modifications may work together to change the behavior of the nucleosome. The idea that multiple dynamic modifications regulate gene transcription in a systematic and reproducible way is called the histone code. The Histone Code is hypothesized to be a code consisting of covalent Histone tail modifications

DNA methylation frequently occurs in repeated sequences, and may help to suppress 'junk DNA':^[9] Because 5-methylcytosine is chemically very similar to thymidine, CpG sites are frequently mutated and become rare in the genome, except at CpG islands where they remain unmethylated. In Molecular biology, junk DNA is a provisional label for the portions of the DNA sequence of a Chromosome or a Genome for which no 5-Methylcytosine is a methylated form of Cytosine in which a Methyl group is attached to carbon 5 altering its structure without altering its base-pairing Thymidine (more precisely called deoxythymidine; can also be labelled deoxyribosylthymine, and thymine deoxyriboside) is a Chemical compound CpG islands are genomic regions that contain a high frequency of CG dinucleotides Epigenetic changes of this type thus have the potential to direct increased frequencies of permanent genetic mutation. DNA methylation patterns are known to be established and modified in response to environmental factors by a complex interplay of at least three independent DNA methyltransferases, DNMT1, DNMT3A and DNMT3B, the loss of any of which is lethal in mice. DNA methylation is a type of chemical modification of DNA that can be inherited and subsequently removed without changing the original DNA sequence In Biochemistry, the DNA methyltransferase (DNA MTase family of Enzymes catalyze the transfer of a Methyl group to DNA. ^[10] DNMT1 is the most abundant methyltransferase in somatic cells,^[11] localizes to replication foci,^[12] has a 10–40-fold preference for hemimethylated DNA and interacts with the proliferating cell nuclear antigen (PCNA). ^[13] By preferentially modifying hemimethylated DNA, DNMT1 transfers patterns of methylation to a newly synthesized strand after DNA replication, and therefore is often referred to as the ‘maintenance' methyltransferase. DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules ^[14] DNMT1 is essential for proper embryonic development, imprinting and X-inactivation. ^[10][15]

Chromosomal regions can adopt stable and heritable alternative states resulting in bistable gene expression without changes to the DNA sequence. Epigenetic control is often associated with alternative covalent modifications of histones. The stability and heritability of states of larger chromosomal regions are often thought to involve positive feedback where modified nucleosomes recruit enzymes that similarly modify nearby nucleosomes. A simplified stochastic model for this type of epigenetics is found here ^[16] .

Because DNA methylation and chromatin remodeling play such a central role in many types of epigenic inheritance, the word "epigenetics" is sometimes used as a synonym for these processes. However, this can be misleading. Chromatin remodeling is not always inherited, and not all epigenetic inheritance involves chromatin remodeling. ^[17]

It has been suggested that the histone code could be mediated by the effect of small RNAs. The Histone Code is hypothesized to be a code consisting of covalent Histone tail modifications The recent discovery and characterization of a vast array of small (21- to 26-nt), non-coding RNAs suggests that there is an RNA component, possibly involved in epigenetic gene regulation. Small interfering RNAs can modulate transcriptional gene expression via epigenetic modulation of targeted promoters. In Biology, a promoter is a region of DNA that facilitates the transcription of a particular Gene. ^[18]

RNA transcripts and their encoded proteins

Sometimes a gene, after being turned on, transcribes a product that (either directly or indirectly) maintains the activity of that gene. For example, Hnf4 and MyoD enhance the transcription of many liver- and muscle-specific genes, respectively, including their own, through the transcription factor activity of the proteins they encode. HNF4 ( H epatocyte N uclear F actor 4 is a Nuclear receptor Protein mostly expressed in the Liver, gut kidney and pancreatic MyoD is a Protein with a key role in regulating Muscle In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Other epigenetic changes are mediated by the production of different splice forms of RNA, or by formation of double-stranded RNA (RNAi). In Molecular biology, splicing is a modification of an RNA after transcription, in which Introns are removed and Exons are joined Ribonucleic acid ( RNA) is a Nucleic acid that consists of a long chain of Nucleotide units RNA interference ( RNAi) is a mechanism that inhibits Gene expression at the stage of translation or by hindering the transcription of specific Descendants of the cell in which the gene was turned on will inherit this activity, even if the original stimulus for gene-activation is no longer present. These genes are most often turned on or off by signal transduction, although in some systems where syncytia or gap junctions are important, RNA may spread directly to other cells or nuclei by diffusion. In Biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another In Biology, a syncytium ( plural syncytia) is a large cell-like structure filled with Cytoplasm containing many nuclei A gap junction or nexus is a specialized Intercellular connection between certain animal cell -types Diffusion is the net movement of particles (typically molecules from an area of high concentration to an area of low concentration by uncoordinated random movement A large amount of RNA and protein is contributed to the zygote by the mother during oogenesis or via nurse cells, resulting in maternal effect phenotypes. For other meanings see Zygote (disambiguation. A zygote (from Greek ζυγωτός zugōtos "joined" or "yoked" Oogenesis or rarely oögenesis is the creation of an Ovum (egg cell The term nurse cell is used in several unrelated ways in different scientific fields Human physiology Nurse cells are specialized macrophages residing in the bone marrow A maternal effect, in genetics is the phenomenon where the Genotype of a mother is expressed in the Phenotype of its offspring unaltered by paternal genetic A smaller quantity of sperm RNA is transmitted from the father, but there is recent evidence that this epigenetic information can lead to visible changes in several generations of offspring. ^[19]

Prions

For more details on this topic, see Prions. A prion (ˈpriːɒn is thought to be an infectious agent that according to current scientific consensus is comprised entirely of a propagated, mis-folded

Prions are infectious forms of proteins. A prion (ˈpriːɒn is thought to be an infectious agent that according to current scientific consensus is comprised entirely of a propagated, mis-folded Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Proteins generally fold into discrete units which perform distinct cellular functions, but some proteins are also capable of forming an infectious conformational state known as a prion. Although often viewed in the context of infectious disease, prions are more loosely defined by their ability to catalytically convert other native state versions of the same protein to an infectious conformational state. Transmissible spongiform encephalopathies' ( TSEs, also known as prion diseases) are a group of progressive conditions that affect the Brain and It is in this latter sense that they can be viewed as epigenetic agents capable of inducing a phenotypic change without a modification of the genome. ^[20]

Fungal prions are considered epigenetic because the infectious phenotype caused by the prion can be inherited without modification of the genome. Fungal Prions have been investigated leading to a deeper understanding of disease-forming Mammalian prions PSI+ and URE3, discovered in yeast in 1965 and 1971, are the two best studied of this type of prion. Fungal Prions have been investigated leading to a deeper understanding of disease-forming Mammalian prions Saccharomyces cerevisiae is a Species of Budding Yeast. It is perhaps the most useful Yeast owing to its use since ancient times ^[21][22] Prions can have a phenotypic effect through the sequestration of protein in aggregates, thereby reducing that protein's activity. In PSI+ cells, the loss of the Sup35 protein (which is involved in termination of translation) causes ribosomes to have a higher rate of read-through of stop codons, an effect which results in suppression of nonsense mutations in other genes. In Genetics, a nonsense mutation is a Point mutation in a sequence of DNA that results in a premature Stop codon, or a nonsense ^[23] The ability of Sup35 to form prions may be a conserved trait. It could confer an adaptive advantage by giving cells the ability to switch into a PSI+ state and express dormant genetic features normally terminated by premature stop codon mutations. ^[24][25]

Structural inheritance systems

For more details on this topic, see Structural inheritance. Structural inheritance is the transmission of a trait in a living Organism by a self-perpetuating spatial structures

In ciliates such as Tetrahymena and Paramecium, genetically identical cells show heritable differences in the patterns of ciliary rows on their cell surface. The ciliates are one of the most important groups of Protists common almost everywhere there is water — lakes ponds oceans rivers and soils with many ectosymbiotic Tetrahymena are free-living Ciliate Protozoa that can also switch from commensalistic to Pathogenic modes of survival Paramecia are a group of Unicellular Ciliate Protozoa formerly known as “slipper Animalcules �� from their Slipper shape are commonly Experimentally altered patterns can be transmitted to daughter cells. It seems existing structures act as templates for new structures. The mechanisms of such inheritance are unclear, but reasons exist to assume that multicellular organisms also use existing cell structures to assemble new ones. ^[26]

Functions and consequences

Development

Somatic epigenetic inheritance, particularly through DNA methylation and chromatin remodeling, is very important in the development of multicellular eukaryotic organisms. The genome sequence is static (with some notable exceptions), but cells differentiate in many different types, which perform different functions, and respond differently to the environment and intercellular signalling. Thus, as individuals develop, morphogens activate or silence genes in an epigenetically heritable fashion, giving cells a "memory". A morphogen is a substance governing the pattern of tissue development and in particular the positions of the various specialized cell types within a tissue In mammals, most cells terminally differentiate, with only stem cells retaining the ability to differentiate into several cell types ("totipotency" and "multipotency"). Stem cells are cells found in most if not all multi-cellular Organisms. In mammals, some stem cells continue producing new differentiated cells throughout life, but mammals are not able to respond to loss of some tissues, for example, the inability to regenerate limbs, which some other animals are capable of. Unlike animals, plant cells do not terminally differentiate, remaining totipotent with the ability to give rise to a new individual plant. While plants do utilise many of the same epigenetic mechanisms as animals, such as chromatin remodeling, it has been hypothesised that plant cells do not have "memories", resetting their gene expression patterns at each cell division using positional information from the environment and surrounding cells to determine their fate. ^[27]

Medicine

Epigenetics has many and varied potential medical applications. Congenital genetic disease is well understood, and it is also clear that epigenetics can play a role, for example, in the case of Angelman syndrome and Prader-Willi syndrome. Angelman syndrome (AS is a neuro- Genetic disorder characterized by intellectual and Developmental delay, sleep disturbance Seizures, jerky movements Prader-Willi syndrome (abbreviated PWS) is a very rare Genetic disorder, in which seven genes (or some subset thereof on chromosome 15 are missing or unexpressed These are normal genetic diseases caused by gene deletions, but are unusually common because individuals are essentially hemizygous because of genomic imprinting, and therefore a single gene knock out is sufficient to cause the disease, where most cases would require both copies to be knocked out. Zygosity refers to the genetic condition of a Zygote. In genetics zygosity describes the similarity or dissimilarity of DNA between Homologous Genomic imprinting is a genetic phenomenon by which certain Genes are expressed in a Parent -of-origin-specific manner ^[28]

Evolution

Although epigenetics in multicellular organisms is generally thought to be a mechanism involved in differentiation, with epigenetic patterns "reset" when organisms reproduce, there have been some observations of transgenerational epigenetic inheritance (e. g. , the phenomenon of paramutation observed in maize). In Epigenetics, paramutation is an interaction between two Alleles of a single locus, resulting in a heritable change of one allele that is induced by the Although most of these multigenerational epigenetic traits are gradually lost over several generations, the possibility remains that multigenerational epigenetics could be another aspect to evolution and adaptation. These effects may require enhancements to the standard conceptual framework of the modern evolutionary synthesis. ^[29][30]

Epigenetic features may play a role in short-term adaptation of species by allowing for reversible phenotype variability. The modification of epigenetic features associated with a region of DNA allows organisms, on a multigenerational time scale, to switch between phenotypes that express and repress that particular gene. ^[31] Whereas the DNA sequence of the region is not mutated, this change is reversible. It has also been speculated that organisms may take advantage of differential mutation rates associated with epigenetic features to control the mutation rates of particular genes. ^[31]

Epigenetic changes have also been observed to occur in response to environmental exposure—for example, mice given some dietary supplements have epigenetic changes affecting expression of the agouti gene, which affects their fur color, weight, and propensity to develop cancer. Agouti signalling peptide, also referred to as Agouti is a Peptide which acts as an antagonist at Melanocortin receptors specifically MC1. ^[32][33]

Epigenetic effects in humans

Genomic imprinting and related disorders

Some human disorders are associated with genomic imprinting, a phenomenon in mammals where the father and mother contribute different epigenetic patterns for specific genomic loci in their germ cells. ^[34] The most well-known case of imprinting in human disorders is that of Angelman syndrome and Prader-Willi syndrome—both can be produced by the same genetic mutation, chromosome 15q partial deletion, and the particular syndrome that will develop depends on whether the mutation is inherited from the child's mother or from their father. Angelman syndrome (AS is a neuro- Genetic disorder characterized by intellectual and Developmental delay, sleep disturbance Seizures, jerky movements Prader-Willi syndrome (abbreviated PWS) is a very rare Genetic disorder, in which seven genes (or some subset thereof on chromosome 15 are missing or unexpressed Chromosome 15q partial deletion is an extremely rare Human Genetic disorder, caused by a chromosomal aberration in which the long ("q" arm of ^[35] This is due to the presence of genomic imprinting in the region. Genomic imprinting is a genetic phenomenon by which certain Genes are expressed in a Parent -of-origin-specific manner Beckwith-Wiedemann syndrome is also associated with genomic imprinting, often caused by abnormalities in maternal genomic imprinting of a region on chromosome 11. Beckwith-Wiedemann syndrome (BWS is an overgrowth disorder present at birth characterized by an increased risk of childhood cancer and certain features

Transgenerational epigenetic observations

Marcus Pembrey and colleagues also observed that the paternal (but not maternal) grandsons of Swedish boys who were exposed to famine in the 19th century were less likely to die of cardiovascular disease; if food was plentiful then diabetes mortality in the grandchildren increased, suggesting that this was a transgenerational epigenetic inheritance. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc ^[36]

Cancer and developmental abnormalities

A variety of compounds are considered as epigenetic carcinogens—they result in an increased incidence of tumors, but they do not show mutagen activity (toxic compounds or pathogens that cause tumors incident to increased regeneration should also be excluded). The term carcinogen refers to any substance Radionuclide or radiation that is an agent directly involved in the promotion of Cancer or in the fatation of its propagation In Biology, a mutagen ( Latin, literally origin of change) is a physical or chemical agent that changes the genetic information (usually DNA) Examples include diethylstilbestrol, arsenite, hexachlorobenzene, and nickel compounds. Diethylstilbestrol ( DES) is a drug, an orally active synthetic nonsteroidal Estrogen that was first synthesized in 1938 The arsenite Ion is As[[Oxygen O]]33&minusAn arsenite (compound is any compound that contains this ion Hexachlorobenzene, or perchlorobenzene, is a chlorinated Hydrocarbon with the molecular formula C6Cl6 Nickel (ˈnɪkəl is a metallic Chemical element with the symbol Ni and Atomic number 28

Many teratogens exert specific effects on the fetus by epigenetic mechanisms. ^[37][38] While epigenetic effects may preserve the effect of a teratogen such as diethylstilbestrol throughout the life of an affected child, the possibility of birth defects resulting from exposure of fathers or in second and succeeding generations of offspring has generally been rejected on theoretical grounds and for lack of evidence. Diethylstilbestrol ( DES) is a drug, an orally active synthetic nonsteroidal Estrogen that was first synthesized in 1938 ^[39] However, a range of male-mediated abnormalities have been demonstrated, and more are likely to exist. ^[40] FDA label information for Vidaza(tm), a formulation of 5-azacitidine (an unmethylatable analog of cytidine that causes hypomethylation when incorporated into DNA) states that "men should be advised not to father a child" while using the drug, citing evidence in treated male mice of reduced fertility, increased embryo loss, and abnormal embryo development. In rats, endocrine differences were observed in offspring of males exposed to morphine. ^[41] In mice, second generation effects of diethylstilbesterol have been described occurring by epigenetic mechanisms. ^[42]

Epigenetics in microorganisms

Bacteria make widespread use of postreplicative DNA methylation for the epigenetic control of DNA-protein interactions. Bacteria make use of DNA adenine methylation (rather than DNA cytosine methylation) as an epigenetic signal. DNA adenine methylation is important in bacteria virulence in organisms such as Escherichia coli, Salmonella, Vibrio, Yersinia, Haemophilus, and Brucella. Salmonella is a Genus of rod-shaped Gram-negative enterobacteria that causes Typhoid fever, Paratyphoid fever Vibrio is a Genus of Gram-negative Bacteria possessing a curved rod shape Yersinia is a Genus of bacteria in the family Enterobacteriaceae. Haemophilus is a Genus of Gram-negative, Pleomorphic, coccobacilli Bacteria belonging to the Pasteurellaceae Brucella is a Genus of Gram-negative bacteria. They are small (0 In Alphaproteobacteria, methylation of adenine regulates the cell cycle and couples gene transcription to DNA replication. The Proteobacteria are a major group ( Phylum) of Bacteria. They include a wide variety of Pathogens such as Escherichia, In Gammaproteobacteria, adenine methylation provides signals for DNA replication, chromosome segregation, mismatch repair, packaging of bacteriophage, transposase activity and regulation of gene expression. Gammaproteobacteria is a class of several medically and scientifically important groups of bacteria such as the Enterobacteriaceae ( Escherichia coli) ^{[43] [44]}

The yeast prion PSI is generated by a conformational change of a translation termination factor, which is then inherited by daughter cells. Yeasts are a growth form of eukaryotic Microorganisms classified in the kingdom Fungi, with about 1500 Species currently described A prion (ˈpriːɒn is thought to be an infectious agent that according to current scientific consensus is comprised entirely of a propagated, mis-folded This can provide a survival advantage under adverse conditions. This is an example of epigenetic regulation enabling unicellular organisms to respond rapidly to environmental stress. Prions can be viewed as epigenetic agents capable of inducing a phenotypic change without modification of the genome. ^[44]

See also

• Histone code
• Baldwinian evolution
• Barbara McClintock
• Centromere
• Evolutionary developmental psychology
• Molecular biology
• Somatic epitype
• Weismann barrier

Further reading

• Oskar Hertwig, 1849-1922. The Histone Code is hypothesized to be a code consisting of covalent Histone tail modifications The Baldwin effect, also known as Baldwinian evolution or ontogenic evolution, is an early evolutionary Theory put forward in 1896 in a paper "A New Barbara McClintock (June 16 1902 – September 2 1992 the 1983 Nobel Laureate in Physiology or Medicine, was an American scientist and one of the world's most distinguished A centromere is a region of DNA typically found near the middle of a Chromosome where two Sister chromatids come in contact Evolutionary developmental psychology, (or EDP) is the application of the basic principles of Darwinian Evolution, particularly Natural selection, to explain Molecular biology is the study of Biology at a molecular level A somatic epitype is a non-heritable Epigenetic alteration in a gene The Weismann barrier is the principle that hereditary information moves only from genes to body cells and never in reverse Oscar Hertwig ( April 21, 1849, Friedberg, Hesse - October 25, 1922, Berlin) was a German Zoologist Biological problem of today: preformation or epigenesis? The basis of a theory of organic development. W. Heinemann: London, 1896. Year 1896 ( MDCCCXCVI) was a Leap year starting on Wednesday (link will display the full calendar of the Gregorian Calendar (or a Leap year
• R. Jaenisch and A. Bird (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat. Genet. 33 (Suppl) 245-254.
• Joshua Lederberg, "The Meaning of Epigenetics", The Scientist 15(18):6, Sep. Joshua Lederberg ( May 23, 1925 &ndash February 2, 2008) was an American molecular biologist known for his work in 17, 2001. Year 2001 ( MMI) was a Common year starting on Monday according to the Gregorian calendar.
• R. J. Sims III, K. Nishioka and D. Reinberg (2003) Histone lysine methylation: a signature for chromatin function. Trends Genet. 19, 629-637.
• Rupert Sheldrake, A New Biology, morphogenetic fields.
• B. D. Strahl and C. D. Allis (2000) The language of covalent histone modifications. Nature 403, 41-45.
• C.H. Waddington (1942), "The epigenotype". Conrad Hal Waddington FRS FRSE (1905&ndash1975 was a developmental Biologist, paleontologist, Geneticist, Embryologist Year 1942 ( MCMXLII) was a Common year starting on Thursday (the link will display the full 1942 calendar of the Gregorian calendar. Endeavour 1, 18–20.
• B. McClintock (1978) Mechanisms that Rapidly Reorganize the Genome. Stadler Symposium vol 10:25-48
• G. W. Grimes; K. J. Aufderheide; Cellular Aspects of Pattern Formation: the Problem of Assembly. Monographs in Developmental Biology, Vol. 22. Karger, Basel (1991)
• Eva Jablonka and Marion J. Lamb Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life The MIT Press (2005) ISBN 978-0262101073
• Article on The Philosophy of Molecular and Developmental Biology to appear in Blackwell’s Guide to Philosophy of Science,. Eva Jablonka (חווה יבלונקה is a theorist and geneticist known especially for her interest in Epigenetic inheritance. Marion J Lamb was Senior Lecturer at Birkbeck University of London, before her retirement P. K. Machamer and M. Silberstein (Eds).
• Epigenetics edited by C. David Allis, Thomas Jenuwein, Danny Reinberg, and Marie-Laure Caparros. Cold Spring Harbor Press, 2007.
• Evolution by Nicholas Barton, Derek Briggs, Jonathan Eisen, David Goldstein, and Nipam Patel. eVolution is the third Album by eLDee, it was due to be released in 2008 Cold Spring Harbor Press, 2007.
• Chromatin and Gene Regulation: Mechanisms in Epigenetics by Bryan Turner. Blackwell Publishing, 2002.
• Survival of the Sickest by Dr. Sharon Moalem with Jonathan Prince, Published 2007
• Epigenetics edited by J. Tost. Caister Academic Press, 2008.
• RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity edited by K. V. Morris. Caister Academic Press, 2008.

Notes and references

External links

• DNA Is Not Destiny - Discover Magazine cover story
• BBC - Horizon - 2005 - The Ghost In Your Genes