Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase

Verreault, A., Kaufman, P. D., Kobayashi, R., Stillman, B. (January 1998) Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1 acetyltransferase. Current Biology, 8 (2). pp. 96-108. ISSN 0960-9822

DOI: 10.1016/S0960-9822(98)70040-5


BACKGROUND: In eukaryotic cells, newly synthesized histone H4 is acetylated at lysines 5 and 12, a transient modification erased by deacetylases shortly after deposition of histones into chromosomes. Genetic studies in Saccharomyces cerevisiae revealed that acetylation of newly synthesized histones H3 and H4 is likely to be important for maintaining cell viability; the precise biochemical function of this acetylation is not known, however. The identification of enzymes mediating site-specific acetylation of H4 at Lys5 and Lys12 may help explain the function of the acetylation of newly synthesized histones. RESULTS: A cDNA encoding the catalytic subunit of the human Hat1 acetyltransferase was cloned and, using specific antibodies, the Hat1 holoenzyme was purified from human 293 cells. The human enzyme acetylates soluble but not nucleosomal H4 at Lys5 and Lys12 and acetylates histone H2A at Lys5. Unexpectedly, we found Hat1 in the nucleus of S-phase cells. Like its yeast counterpart, the human holoenzyme consists of two subunits: a catalytic subunit, Hat1, and a subunit that binds core histones, p46, which greatly stimulates the acetyltransferase activity of Hat1. Both p46 and the highly related p48 polypeptide (the small subunit of human chromatin assembly factor 1; CAF-1) bind directly to helix 1 of histone H4, a region that is not accessible when H4 is in chromatin. CONCLUSIONS: We suggest that p46 and p48 are core-histone-binding subunits that target chromatin assembly factors, chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA.

Item Type: Paper
Uncontrolled Keywords: Acetylation Acetyltransferases genetics metabolism Amino Acid Sequence Animals Base Sequence Binding Sites COS Cells Cell Nucleus metabolism Coenzymes isolation & purification DNA metabolism DNA Complementary Histones metabolism Humans Lysine metabolism Molecular Sequence Data Nucleosomes metabolism Protein Folding Research Support Non-U.S. Gov't Research Support U.S. Gov't, P.H.S. S Phase Sequence Homology Amino Acid
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > histone
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: CSHL Librarian
Date: 15 January 1998
Date Deposited: 17 Feb 2012 20:28
Last Modified: 20 Jun 2017 19:30
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