- Histone acetylation and deacetylation
In histone acetylation and deacetylation, the
histonesare acetylated and deacetylated on lysineresidues in the N-terminal tail and on the surface of the nucleosomecore as part of gene regulation. Typically, these reactions are catalyzed by enzymes with " histone acetyltransferase" (HAT) or " histone deacetylase" (HDAC) activity. The source of the acetyl group in histone acetylation is Acetyl-Coenzyme A, and in histone deacetylation the acetyl group is transferred to Coenzyme A.
Acetylated histones and nucleosomes represent a type of
epigenetictag within chromatin. Acetylation brings in a negative charge, acting to neutralise the positive charge on the histones and decreases the interaction of the N termini of histones with the negatively charged phosphate groups of DNA. As a consequence, the condensed chromatin is transformed into a more relaxed structure which is associated with greater levels of gene transcription. This relaxation can be reversed by HDAC activity. Relaxed, transcriptionally active DNA is referred to as euchromatin. More condensed (tightly packed) DNA is referred to as heterochromatin. Condensation can be brought about by processes including deacetylation and methylation; the action of methylation is indirect and has no effect upon charge.
This charge neutralization model has been challenged by recent studies, according to which transcriptionally active genes are correlated with rapid turnover of histone acetylation. This requires that the HATs and HDACs must act continuously on the affected histone tail. Methylation at a specific lysine residue (K4) is involved in targeting histone tails for continuous acetylation and deacetylation.
* Animation of histone tail acetylation and deacetylation: http://www.broad.harvard.edu/chembio/lab_schreiber/anims/animations/smdbHDAC.php
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