title: Effects of acetylation of histone H4 at lysines 8 and 16 on activity of the Hat1 histone acetyltransferase.
abstract: During nucleosome assembly in vivo, newly synthesized histone H4 is specifically diacetylated on lysines 5 and 12 within the H4 NH(2)-terminal tail domain. The highly conserved "K5/K12" deposition pattern of acetylation is thought to be generated by the Hat1 histone acetyltransferase, which in vivo is found in the HAT-B complex. In the following report, the activity and substrate specificity of the human HAT-B complex and of recombinant yeast Hat1p have been examined, using synthetic H4 NH(2)-terminal peptides as substrates. As expected, the unacetylated H4 peptide was a good substrate for acetylation by yeast Hat1p and human HAT-B, while the K5/K12-diacetylated peptide was not significantly acetylated. Notably, an H4 peptide previously diacetylated on lysines 8 and 16 was a very poor substrate for acetylation by either yeast Hat1p or human HAT-B. Treating the K8/K16-diacetylated peptide with histone deacetylase prior to the HAT-B reaction raised acetylation at K5/K12 to 70-80% of control levels. These results present strong support for the model of H4-Hat1p interaction proposed by Dutnall et al. (Dutnall, R. N., Tafrov, S. T., Sternglanz, R., and Ramakrishnan, V. (1998) Cell 94, 427-438) and provide evidence for the first time that site-specific acetylation of histones can regulate the acetylation of other substrate sites.
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Makowski
authors.forename: R N
authors.initials: RN
authors.lastname: Dutnall
authors.forename: A T
authors.initials: AT
authors.lastname: Annunziato
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D006657:Histones; D011994:Recombinant Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C110880:histone acetyltransferase type B complex; D008239:Lysine