Dissecting the Molecular Roles of Histone Chaperones in Histone Acetylation by Type B Histone Acetyltransferases (HAT-B)
| Autor: | Ronen Marmorstein, Allison Haigney, M. Daniel Ricketts |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Acetylation
Cell Cycle Proteins Cell Biology Biology environment and public health Biochemistry Histones Histone H4 Histone H1 Multienzyme Complexes Histone methyltransferase Mutation parasitic diseases Histone H2A Humans Histone code Gene Regulation Histone octamer HAT1 Molecular Biology Histone Acetyltransferases Molecular Chaperones Histone binding |
| Zdroj: | Journal of Biological Chemistry. 290:30648-30657 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m115.688523 |
| Popis: | The HAT-B enzyme complex is responsible for acetylating newly synthesized histone H4 on lysines K5 and K12. HAT-B is a multisubunit complex composed of the histone acetyltransferase 1 (Hat1) catalytic subunit and the Hat2 (rbap46) histone chaperone. Hat1 is predominantly localized in the nucleus as a member of a trimeric NuB4 complex containing Hat1, Hat2, and a histone H3-H4 specific histone chaperone called Hif1 (NASP). In addition to Hif1 and Hat2, Hat1 interacts with Asf1 (anti-silencing function 1), a histone chaperone that has been reported to be involved in both replication-dependent and -independent chromatin assembly. To elucidate the molecular roles of the Hif1 and Asf1 histone chaperones in HAT-B histone binding and acetyltransferase activity, we have characterized the stoichiometry and binding mode of Hif1 and Asf1 to HAT-B and the effect of this binding on the enzymatic activity of HAT-B. We find that Hif1 and Asf1 bind through different modes and independently to HAT-B, whereby Hif1 binds directly to Hat2, and Asf1 is only capable of interactions with HAT-B through contacts with histones H3-H4. We also demonstrate that HAT-B is significantly more active against an intact H3-H4 heterodimer over a histone H4 peptide, independent of either Hif1 or Asf1 binding. Mutational studies further demonstrate that HAT-B binding to the histone tail regions is not sufficient for this enhanced activity. Based on these data, we propose a model for HAT-B/histone chaperone assembly and acetylation of H3-H4 complexes. |
| Databáze: | OpenAIRE |
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