Bivalent interaction of the PZP domain of BRPF1 with the nucleosome impacts chromatin dynamics and acetylation.
Bivalent interaction of the PZP domain of BRPF1 with the nucleosome impacts chromatin dynamics and acetylation.
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DOI：
10.1093/nar/gkv1321
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发表时间：
2016-01-08
影响因子：
14.9
通讯作者：
Kutateladze TG
中科院分区：
文献类型：
--
作者：
Klein BJ;Muthurajan UM;Lalonde ME;Gibson MD;Andrews FH;Hepler M;Machida S;Yan K;Kurumizaka H;Poirier MG;Côté J;Luger K;Kutateladze TG
BRPF 1（布罗莫结构域PHD指1）是MOZ组蛋白乙酰转移酶（HAT）复合物的核心亚基，对正常发育程序至关重要，并与急性白血病有关。BRPF 1含有一个独特的锌指组装体，称为PZP结构域，其生理作用尚不清楚。在这里，我们阐明了这种新的表观遗传读者的结构-功能关系，并详细说明其与核小体相互作用的生物学和机械后果。PZP具有球形结构，并与核小体形成2：1化学计量复合物，与组蛋白H3和DNA相互作用。这种结合影响核小体动力学，将DNA解包/重包平衡向解包状态转移，并增加DNA可及性。我们证明了BRPF 1 PZP结构域的DNA结合功能是MOZ-BRPF 1-ING 5-hEaf 6 HAT复合物被招募到染色质和乙酰化核小体组蛋白所必需的。我们的研究结果揭示了染色质动力学和MOZ介导的乙酰化之间的新联系。
BRPF1 (bromodomain PHD finger 1) is a core subunit of the MOZ histone acetyltransferase (HAT) complex, critical for normal developmental programs and implicated in acute leukemias. BRPF1 contains a unique assembly of zinc fingers, termed a PZP domain, the physiological role of which remains unclear. Here, we elucidate the structure-function relationship of this novel epigenetic reader and detail the biological and mechanistic consequences of its interaction with nucleosomes. PZP has a globular architecture and forms a 2:1 stoichiometry complex with the nucleosome, bivalently interacting with histone H3 and DNA. This binding impacts the nucleosome dynamics, shifting the DNA unwrapping/rewrapping equilibrium toward the unwrapped state and increasing DNA accessibility. We demonstrate that the DNA-binding function of the BRPF1 PZP domain is required for the MOZ-BRPF1-ING5-hEaf6 HAT complex to be recruited to chromatin and to acetylate nucleosomal histones. Our findings reveal a novel link between chromatin dynamics and MOZ-mediated acetylation.