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Epigenetics
Epigenetics can be defined as acquired changes in chromatin structure that arise independently of a change in the underlying DNA nucleotide sequence. Epigenetic modifications - including acetylation, methylation, phosphorylation, and ubiquitination amongst others - alter the accessibility of DNA to transcription machinery and therefore influence gene expression. Ongoing research is revealing the extent of the influence of epigenetics in disease states, and continues to provide a wealth of novel therapeutic targets.
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Epigenetic mechanisms integrate environmental changes at the cellular level and enable cellular plasticity. As a result, they are involved in pathologies related to diet, lifestyle and environmental exposure to toxins, including cancer, inflammation and metabolic disorders. Proteins that carry out these epigenetic modifications can be thought of as being either "writers", "readers" or "erasers".
Epigenetic writers »
More Information »Epigenetic writers catalyze the addition of chemical groups onto either histone tails or the DNA itself. These modifications are known as epigenetic marks.
Epigenetic readers »
More Information »Epigenetic reader domains can be thought of as effector proteins that recognize and are recruited to specific epigenetic marks. "Writer" and "eraser" enzymes may also contain such reader domains, leading to the coordination of "read-write" or "read-erase" mechanisms.
Epigenetic erasers »
More Information »Epigenetic marks are not necessarily permanent modifications; instead, they can be removed by a group of enzymes known as "erasers" in order to reverse the influence of a given epigenetic mark on gene expression.
| Epigenetic Mechanism | "Writer" Enzymes | "Reader" Domains | "Eraser" Enzymes |
|---|
| DNA Methylation | DNA Methyltransferases | Methyl-CpG binding domains | Active DNA demethylation (enzymes unknown), passive DNA demethylation (passive process) | |
| Histone Lysine Methylation | Protein Lysine Methyltransferases (PKMTs) | Chromodomains; Tudor domains; PHD fingers; MBT domains; Bromodomains; ZF-CW proteins; WD40; PWWP | Histone demethylases | |
| Histone Arginine Methylation | Protein Arginine Methyltransferases (PRMTs) | Tudor domains (recognize symmetrically dimethylated arginines) | Histone demethylases; peptidyl arginine deiminases (PADIs) (putative) | |
| Histone Phosphorylation | Kinases (JAK2, ATM/ATR, PKC, Haspin, Aurora B kinase) | Chromoshadow domains (phosphoTyrosine); 14-3-3 proteins (phosphoSerine); BRCT proteins | Protein tyrosine phosphatases; protein serine/threonine phosphatases | |
| Histone Ubiquitination | Ubiquitin E2 conjugases, ubiquitin E3 ligases | Unknown | Ubiquitin-specific proteases | |
| Histone Acetylation | Histone acetyltransferases | Tandem bromodomains; tandem PHD fingers | Histone deacetylases | |
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Cancer Research Guide
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Epigenetics Research Bulletin
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Checkpoint Kinases & the DNA Damage Response
Written by Michelle D. Garrett and Ian Collins
A summary of the response of the checkpoint kinase signaling network to DNA damage, including activation of DNA repair, cell-cycle arrest, senescence and apoptosis.
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