Histone H4 acetylation distinguishes coding regions of the human genome from heterochromatin in a differentiation-dependent but transcription-independent manner.

Abstract

By immunoprecipitation of chromatin fragments from cultured human HL-60 cells with antibodies specific for H4 acetylated at specific lysine residues we have defined the level of H4 acetylation within transcriptionally active and inactive regions of the genome. H4 within or adjacent to coding regions had a similar level of overall acetylation to input (bulk) chromatin and a similar pattern of acetylation of individual lysines (i.e. 16 > 8, 12 > 5). The acetylation of H4 in coding (and adjacent) regions was not correlated with transcriptional activity and did not vary with position along the constitutively active c-myc gene. Turnover of H4 acetates was not selectively increased in transcriptionally active chromatin. H4 associated with centric heterochromatin or with the CCCTAA repeat of telomeric heterochromatin was infrequently acetylated (< 1%) at all lysines. We conclude that nucleosomes containing acetylated H4 are scattered infrequently and possibly randomly through coding and adjacent regions and are essentially absent from heterochromatin. Induction of differentiation of HL-60 cells by exposure to dimethylsulfoxide or 12-o-tetradecanoylphorbol 13-acetate (TPA) did not alter the level of H4 acetylation within either the c-myc or c-fos genes or other coding regions, but did induce a transient increase in H4 acetylation within centric heterochromatin.