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Epigenetic regulation of gene expression
Stable Identifier
R-HSA-212165
Type
Pathway
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
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Gene expression (Transcription) (Homo sapiens)
Epigenetic regulation of gene expression (Homo sapiens)
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Epigenetic processes regulate gene expression by modulating the frequency, rate, or extent of gene expression in a mitotically or meiotically heritable way that does not entail a change in the DNA sequence. Originally the definition applied only to heritability across generations but later also encompassed the heritable changes that occur during cellular differentiation within one organism.
Molecular analysis shows epigenetic changes comprise covalent modifications, such as methylation and acetylation, to DNA and histones. RNA interference has been implicated in the initiation of some epigenetic changes, for example transcriptional silencing of transposons. Proteins which bind to the modified DNA and histones are then responsible for repressing transcription and for maintaining the epigenetic modifications during cell division.
During differentiation, patterns of gene expression are established by polycomb complexes PRC1 and PRC2. PRC2 methylates histones and DNA to produce the initial marks of repression: trimethylated lysine-27 on histone H3 (H3K27me3) and 5-methylcytosine in DNA. PRC2, through its component EZH2 or, in some complexes, EZH1 trimethylates lysine-27 of histone H3. The H3K27me3 produced by PRC2 is bound by the Polycomb subunit of PRC1. PRC1 ubiquitinates histone H2A and maintains repression.
PRC2 and other epigenetic systems modulate gene expression through DNA methyation, the transfer of a methyl group from S-adenosylmethionine to the 5 position of cytosine in DNA by a family of DNA methyltransferases (DNMTs): DNMT1, DNMT3A, and DNMT3B.
In the reverse process TET1,2,3 and TDG demethylate DNA through the oxidation of the methyl group of 5-methylcytosine by TET enzymes and the excision of the oxidized product (5-formylcytosine or 5-carboxylcytosine) by TDG.
Ribosomal RNA (rRNA) genes are activated and deactivated according to the metabolic requirements of the cell. Positive epigenetic regulation of rRNA expression occurs through chromatin modifications produced by activators such as ERCC6 (CSB), the B-WICH complex, and histone acetylases such as KAT2B (PCAF). Negative epigenetic regulation of rRNA expression occurs through chromatin modifications produced by repressors such as the eNoSC complex, SIRT1, and the NoRC complex.
WDR5 is a component of six histone methyltransferases and three histone acetyltransferases involved in epigenetic regulation of gene expression (reviewed in Guarnaccia and Tansey 2018).
Literature References
PubMed ID
Title
Journal
Year
29385767
Moonlighting with WDR5: A Cellular Multitasker
Tansey, WP
,
Guarnaccia, AD
J Clin Med
2018
12610534
Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals
Bird, A
,
Jaenisch, R
Nat. Genet.
2003
Participants
Events
PRC2 methylates histones and DNA
(Homo sapiens)
TET1,2,3 and TDG demethylate DNA
(Homo sapiens)
Positive epigenetic regulation of rRNA expression
(Homo sapiens)
Negative epigenetic regulation of rRNA expression
(Homo sapiens)
DNA methylation
(Homo sapiens)
Formation of WDR5-containing histone-modifying complexes
(Homo sapiens)
Participates
as an event of
Gene expression (Transcription) (Homo sapiens)
Event Information
Go Biological Process
regulation of gene expression, epigenetic (0040029)
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Epigenetic regulation of gene expression (Bos taurus)
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Epigenetic regulation of gene expression (Danio rerio)
Epigenetic regulation of gene expression (Dictyostelium discoideum)
Epigenetic regulation of gene expression (Drosophila melanogaster)
Epigenetic regulation of gene expression (Gallus gallus)
Epigenetic regulation of gene expression (Mus musculus)
Epigenetic regulation of gene expression (Plasmodium falciparum)
Epigenetic regulation of gene expression (Rattus norvegicus)
Epigenetic regulation of gene expression (Saccharomyces cerevisiae)
Epigenetic regulation of gene expression (Schizosaccharomyces pombe)
Epigenetic regulation of gene expression (Sus scrofa)
Epigenetic regulation of gene expression (Xenopus tropicalis)
Authored
May, B (2008-02-09)
Gopinathrao, G (2008-02-09)
Reviewed
Matthews, L (2014-02-26)
Created
May, B (2008-02-09)
Gopinathrao, G (2008-02-09)
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