HISTONE H4 ACETYLATION DISTINGUISHES CODING REGIONS OF THE HUMAN GENOME FROM HETEROCHROMATIN IN A DIFFERENTIATION-DEPENDENT BUT TRANSCRIPTION-INDEPENDENT MANNER

By immunoprecipitation of chromatin fragments from cultured human HL-6 0 cells with antibodies specific for H4 acetylated at specific lysine residues we have defined the level of H4 acetylation within transcript ionally active and inactive regions of the genome, H4 within or adjace nt to coding regions had a similar level of overall acetylation to inp ut (bulk) chromatin and a similar pattern of acetylation of individual lysines (i.e. 16 > 8, 12 > 5). The acetylation of H4 in coding (and a djacent) 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 transcriptio nally active chromatin, H4 associated with centric heterochromatin or with the CCCTAA repeat of telomeric heterochromatin was infrequently a cetylated (<1%) at all lysines. We conclude that nucleosomes containin g acetylated H4 are scattered infrequently and possibly randomly throu gh coding and adjacent regions and are essentially absent from heteroc hromatin. Induction of differentiation of HL-60 cells by exposure to d imethylsulfoxide or 12-o-tetradecanoylphorbol W-acetate (TPA) did not alter the level of H4 acetylation within either the c-myc or c-fos gen es or other coding regions, but did induce a transient increase in H4 acetylation within centric heterochromatin.