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What is epigenetics?
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Definition
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Nucleosome etched in crystal Epigenetics refers to DNA and chromatin modifications that persist from one cell division to the next despite a lack of change in the underlying DNA sequence. Some epigenetic changes show transgenerational inheritance meaning that these changes can be passed from one generation to the next. Epigenetics plays an important role in cellular differentiation, allowing dinstict0 b) J+ d$ K. N) }8 R
cell types to have specific characteristics despite sharing the same DNA sequence. Some examples of epigenetic processes include imprinting, bookmarking, gene silencing, paramutation, X chromosome inactivation, reprogramming, position effect, histone modifications and heterochromatin, some carcinogenesis, maternal effects, and transvection. The epigenome refers to the overall epigenetic state of a cell while the epigenetic code refers to epigenetic features such as DNA methylation and histone modifications that create different phenotypes in different cells. & h- Y7 e) @0 Q" C) M# M5 i
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% i! ~+ K5 a4 P0 O; fEpigenetic mechanisms5 m2 {# T1 A* q, m
The mechanisms of epigenetic inheritance systems are still being unraveled, but our current understanding has uncovered at least 4 routes by which epigenetic changes persist over time. These routes include RNA transcripts, cellular structures, DNA methylation/chromatin remodeling, and even prions: " l8 d# |* c9 y: _$ X- a9 r$ J" I
/ o" C( ?! t. F! w# WThe expression of certain genes can enhance the production of other similar genes, and even the gene itself. The enhanced expression of certain genes can be inherited by subsequent descendents. This can be through transcription factors and signal transduction pathways; in systems containing gap junctions, the actual mRNA may be spread to other cells or nuclei via diffusion. During oogenesis, a large amount of RNA and protein is contributed to the zygote by the mother, leading to maternal effect phenotypes. & R# L J" e2 @: C V- E
( v4 I0 z y+ p- P+ oStructural inheritance is common in ciliates such as paramecium where the pattern of ciliary rows is inherited from one generation to the next. The existing structure of the ciliary rows acts as a template for new structures.
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Histones
1 V S; e& D7 H- g, {; WDNA associates with histones to form chromatin. Gene expression can be regulated through chromatin remodeling which arises from either post-translational modification of histones or DNA methylation (conversion of cytosine to 5-methylcytosine). Histone tails are the most heavily modified region, and modifications include acetylation, methylation, and ubiquitylation. Histone acetylation by histone acetyltranferase enzymes (HATs) are associated with transcriptional competence. This series of histone modifications is known as the histone code. Now, nucelosomes (DNA complexed with histones) are not totally removed during DNA replication and the modified histones can act as a template, allowing for inheritance of histone modifications in the daughter cell. DNA methylation often occurs in repetitive DNA sequences and acts to suppress "junk" DNA. The most common type of methylation event is the methylation at the 5' position of cytosine. In adult tissue, methylation usually occurs at CpG dinucleotide sites while in embryonic stem cells, this dinucleotide propensity is not important. The resulting 5-methylcytosine residues are more susceptible to mutation and therefore CpG regions are relatively rare except in CpG islands which are composed of long (300-3000 bp) stretches of GC nucleotides and are in or near 40% of promoters of mammalian genes. These CpG islands are less likely to be methylated. DNA methylation patterns are determined by an interplay between the environment and 3 independent DNA methyltransferases (DNMT1, DNMT3A, DNMT3B). Histone deacetylation is depicted in the above video. - e$ o( w3 E- ~, _
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0 f# _9 G1 r5 Y, T/ E( {Importance of epigenetics9 g- R1 m4 \$ y" H8 n, O
Epigenetics is important in development partly because the genome is largely static. Epigenetic modifications are required to provide some dynamic variability to cellular function and phenotype, allowing for cellular differentiation. Epigenetics can also contribute to congenital disorders such as Angelman syndrome and Prader-Willi syndrome. Epigenetics may also be important in evolution since transgenerational inheritance of epigenetic modifications has been observed (eg, paramutation in maize). Often however, these modifications are lost after several generations. |
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