title: The accessibility of histone H3 tails in chromatin modulates their acetylation by P300/CBP-associated factor.
abstract: P300/CBP-associated factor (PCAF) is a transcriptional coactivator with intrinsic histone acetylase activity. Reversible acetylation of the core histone tails in chromatin has been linked to transcriptional regulation. Here we investigate the mechanism whereby PCAF acetylates its target in chromatin. We demonstrate that recombinant PACF preferentially acetylates the H3 tail in oligonucleosomes, as compared with nucleosome core particles. The rate of acetylation is directly related to the length of the oligonucleosomal substrate. Using a trypsin accessibility assay, we demonstrate that the rate of acetylation is also related to the accessibility of the H3 tail in uncondensed oligonucleosomes. We suggest that PCAF, and perhaps other histone acetyltransferases, acetylate chromatin templates more efficiently than core particle subunits and that this preference arises from an increased accessibility of the H3 tail in either condensed or uncondensed oligonucleosomes. Acetylation of the H3 tails by the native PCAF complex is not affected by the length of the oligonucleosomal substrate. Our results suggest that the accessibility of the H3 tail in chromatin is a major factor affecting their rate of acetylation and that component(s) in the native PCAF complex function to modify the organization of these tails in chromatin thereby enhancing their accessibility to PCAF.
authors.affiliation: Protein Section, Laboratory of Metabolism, Division of Basic Science, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. herr@helix.nih.gov
authors.forename: J E
authors.initials: JE
authors.lastname: Herrera
authors.forename: R L
authors.initials: RL
authors.lastname: Schiltz
authors.forename: M
authors.initials: M
authors.lastname: Bustin
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002645:Chickens; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D051548:Histone Acetyltransferases; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008836:Micrococcal Nuclease / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors; D015533:Transcriptional Activation; D014357:Trypsin / Q000494:pharmacology; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002843:Chromatin; D051548:Histone Acetyltransferases; D006657:Histones; D008274:Magnesium; D008836:Micrococcal Nuclease; D009707:Nucleosomes; D011994:Recombinant Proteins; D014157:Transcription Factors; D014357:Trypsin; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor