CENP-B protects centromere chromatin integrity by facilitating histone deposition via the H3.3-specific chaperone Daxx.
CENP-B protects centromere chromatin integrity by facilitating histone deposition via the H3.3-specific chaperone Daxx.
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DOI：
10.1186/s13072-017-0164-y
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发表时间：
2017-12-22
影响因子：
3.9
通讯作者：
Ishov AM
中科院分区：
文献类型：
--
作者：
Morozov VM;Giovinazzi S;Ishov AM
主要的染色质单位，核小体，可以通过掺入组蛋白变体来调节，所述组蛋白变体与翻译后组蛋白修饰组合，决定染色质的表观遗传学性质。了解在不同基因组元件处产生组蛋白变体景观的机制有望提高我们对染色质组装和功能的理解。Daxx分子伴侣将转录相关的组蛋白H3.3沉积在着丝粒上，但着丝粒特异性Daxx靶向的机制仍不清楚。在这项研究中，我们确定了一个意想不到的功能的组成型着丝粒蛋白CENP-B，作为一个“信标”的H3.3掺入。CENP-B缺失减少了着丝粒处的Daxx缔合和H3.3掺入。Daxx/CENP-B相互作用和Daxx着丝粒缔合是SUMO依赖性的，并且需要Daxx的西姆斯。SUMO-2而不是SUMO-1的消耗降低了Daxx/CENP-B相互作用并降低了Daxx和H3.3的着丝粒积累，证明了SUMO旁系同源物在H3.3伴侣中的不同功能。最后，CENP-B/Daxx依赖性H3.3途径的破坏使着丝粒处的异染色质标记H3 K9 me 3、ATRX和HP 1 α失调，并增加染色体不稳定性。CENP-B和SUMO-2在H3.3负载中的作用揭示了控制染色质维持和基因组稳定性的新机制。鉴于CENP-B是唯一结合着丝粒特异性DNA元件的着丝粒蛋白，我们的研究提供了着丝粒DNA和着丝粒染色质独特的表观遗传景观之间的新联系。本文的在线版本（10.1186/s13072-017-0164-y）包含补充材料，可供授权用户使用。
The main chromatin unit, the nucleosome, can be modulated by the incorporation of histone variants that, in combination with posttranslational histones modifications, determine epigenetics properties of chromatin. Understanding the mechanism that creates a histone variants landscape at different genomic elements is expected to elevate our comprehension of chromatin assembly and function. The Daxx chaperone deposits transcription-associated histone H3.3 at centromeres, but mechanism of centromere-specific Daxx targeting remains unclear. In this study, we identified an unexpected function of the constitutive centromeric protein CENP-B that serves as a “beacon” for H3.3 incorporation. CENP-B depletion reduces Daxx association and H3.3 incorporation at centromeres. Daxx/CENP-B interaction and Daxx centromeric association are SUMO dependent and requires SIMs of Daxx. Depletion of SUMO-2, but not SUMO-1, decreases Daxx/CENP-B interaction and reduces centromeric accumulation of Daxx and H3.3, demonstrating distinct functions of SUMO paralogs in H3.3 chaperoning. Finally, disruption of CENP-B/Daxx-dependent H3.3 pathway deregulates heterochromatin marks H3K9me3, ATRX and HP1α at centromeres and elevates chromosome instability. The demonstrated roles of CENP-B and SUMO-2 in H3.3 loading reveal a novel mechanism controlling chromatin maintenance and genome stability. Given that CENP-B is the only centromere protein that binds centromere-specific DNA elements, our study provides a new link between centromere DNA and unique epigenetic landscape of centromere chromatin. The online version of this article (10.1186/s13072-017-0164-y) contains supplementary material, which is available to authorized users.
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影响因子：
10.5
作者：
Drane, Pascal;Ouararhni, Khalid;Hamiche, Ali
通讯作者：
Hamiche, Ali
DOI：
10.1073/pnas.172403699
发表时间：
2002-12-10
影响因子：
11.1
作者：
Ahmad, K;Henikoff, S
通讯作者：
Henikoff, S
影响因子：
4
作者：
Grewal, Shiv I. S.
通讯作者：
Grewal, Shiv I. S.
影响因子：
7.3
作者：
Golebiowski, Filip;Matic, Ivan;Hay, Ronald T.
通讯作者：
Hay, Ronald T.
DOI：
10.1073/pnas.0600803103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Hake, SB;Allis, CD
通讯作者：
Allis, CD