CoachThe residues of the histone tails are covalently modified: acetylation of lysines (which neutralises their positive charge and loosens the grip on DNA), methylation of lysines and arginines (one, two or three methyl groups, with no change of charge), phosphorylation of serines, ubiquitination of lysines. A modification is named by histone, residue and group: H3K4me3 is histone H3, lysine 4, trimethylated; H3K27ac is H3 lysine 27 acetylated. The histone code is the correlation between combinations of marks and the state of the underlying gene: H3K4me3 and H3K27ac at active promoters and enhancers, H3K36me3 along transcribed gene bodies, H3K9me3 on constitutive heterochromatin, H3K27me3 on genes silenced during development. Enzymes that add a mark are writers (histone acetyltransferases, HATs; methyltransferases), enzymes that remove it are erasers (histone deacetylases, HDACs; demethylases), and proteins that bind a mark and act on it are readers: a bromodomain binds acetyl-lysine, a chromodomain methyl-lysine.
উদাহরণ
Example 1.11 (Numbers)
Measured values for mammalian cells are and per division at a typical CpG. Then , close to the genome-wide methylated fraction, and : a fully methylated site left to the machinery alone would be half-way back to the average after divisions. A silenced promoter that stays silent for the hundreds of divisions of a lifetime therefore needs more than DNMT1: the methyl-CpG readers recruit H3K9 methylation and the H3K9 readers recruit DNMT3, so that a dense island of marks raises its own toward and lowers the neighbouring toward . Conversely, a cell that loses DNMT1 loses the mark passively: with the fraction of methylated strands halves at each division.