The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3
The death-associated protein DAXX is a novel histone chaperone involved in the replication-independent deposition of H3.3
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DOI：
10.1101/gad.566910
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发表时间：
2010-06-15
影响因子：
10.5
通讯作者：
Hamiche, Ali
中科院分区：
文献类型：
--
作者：
Drane, Pascal;Ouararhni, Khalid;Hamiche, Ali
组蛋白变异体H3.3通过取代传统的组蛋白H3.1标记活性染色质。在本研究中，我们研究了H3.3复制无关沉积的详细机制。我们发现死亡结构域相关蛋白DAXX和染色质重塑因子ATRX(阿尔法地中海贫血/智力低下综合征蛋白)与H3.3的沉积机制特异相关。在细菌中表达的DAXX对H3.3具有明显的结合偏好，并有助于(H3.3-H4)(2)四聚体在裸DNA上沉积，从而表明DAXX是H3.3组蛋白伴侣。在DAXX耗竭的细胞中，发现一小部分H3.3与复制依赖的沉积机制有关，这表明细胞适应耗竭。在这些细胞中重新引入的DAXX与H3.3共同定位于早幼粒细胞白血病蛋白(PML)小体。此外，DAXX与着丝粒周围DNA重复序列结合，并通过组装H3.3核小体来调节这些重复序列的转录。这些发现建立了PML小体和着丝粒周围DNA重复染色质结构调节之间的新联系。综上所述，我们的数据表明DAXX作为一个真正的组蛋白伴侣参与了H3.3的复制独立沉积。
The histone variant H3.3 marks active chromatin by replacing the conventional histone H3.1. In this study, we investigate the detailed mechanism of H3.3 replication-independent deposition. We found that the death domain-associated protein DAXX and the chromatin remodeling factor ATRX (alpha-thalassemia/mental retardation syndrome protein) are specifically associated with the H3.3 deposition machinery. Bacterially expressed DAXX has a marked binding preference for H3.3 and assists the deposition of (H3.3-H4)(2) tetramers on naked DNA, thus showing that DAXX is a H3.3 histone chaperone. In DAXX-depleted cells, a fraction of H3.3 was found associated with the replication-dependent machinery of deposition, suggesting that cells adapt to the depletion. The reintroduced DAXX in these cells colocalizes with H3.3 into the promyelocytic leukemia protein (PML) bodies. Moreover, DAXX associates with pericentric DNA repeats, and modulates the transcription from these repeats through assembly of H3.3 nucleosomes. These findings establish a new link between the PML bodies and the regulation of pericentric DNA repeat chromatin structure. Taken together, our data demonstrate that DAXX functions as a bona fide histone chaperone involved in the replication-independent deposition of H3.3.