Histones in transit: Cytosolic histone complexes and diacetylation of H4 during nucleosome assembly in human cells

L. Chang, S. S. Loranger, C. Mizzen, S. G. Ernst, C. D. Allis, A. T. Annunziato

Research output: Contribution to journalArticle

Abstract

The organization and acetylation of nascent histones prior to their stable incorporation into chromatin were examined. Through sedimentation and immunoprecipitation analyses of HeLa cytosolic extracts, two somatic non- nucleosomal histone complexes were detected: one containing nascent H3 and H4, and a second containing H2A (and probably H2B) in association with the nonhistone protein NAP-1. The H3/H4 complex has a sedimentation coefficient of 5-6S, consistent with the presence of one or more escort proteins. H4 in the cytosolic H3/H4 complex is diacetylated, fully in accord with the acetylation state of newly synthesized H4 in chromatin. The diacetylation of nascent human H4 is therefore completed prior to nucleosome assembly. As part of our studies of the nascent H3/H4 complex, the cytoplasmic histone acetyltransferase most likely responsible for acetylating newly synthesized H4 was also investigated. HeLa histone acetyltransferase B (HAT B) acetylates H4 but not H3 in vitro, and maximally diacetylates H4 even in the presence of sodium butyrate. Human HAT B acetylates H4 exclusively on the lysine residues at positions 5 and 12, in complete agreement with the highly conserved acetylation pattern of nascent nucleosomal H4 (Sobel et al., 1995), and has a native molecular weight of ~100 kDa. Based on our findings a model is presented for the involvement of histone acetylation and NAP-1 in H2A/H2B deposition and exchange, during nucleosome assembly and chromatin remodeling in vivo.

Original languageEnglish (US)
Pages (from-to)469-480
Number of pages12
JournalBiochemistry
Volume36
Issue number3
DOIs
StatePublished - Jan 21 1997

ASJC Scopus subject areas

  • Biochemistry

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    Chang, L., Loranger, S. S., Mizzen, C., Ernst, S. G., Allis, C. D., & Annunziato, A. T. (1997). Histones in transit: Cytosolic histone complexes and diacetylation of H4 during nucleosome assembly in human cells. Biochemistry, 36(3), 469-480. https://doi.org/10.1021/bi962069i