Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells.
Hira-dependent histone H3.3 deposition facilitates PRC2 recruitment at developmental loci in ES cells.
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DOI：
10.1016/j.cell.2013.08.061
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发表时间：
2013-09-26
期刊：
影响因子：
64.5
通讯作者：
Allis CD
中科院分区：
文献类型：
--
作者：
Banaszynski LA;Wen D;Dewell S;Whitcomb SJ;Lin M;Diaz N;Elsässer SJ;Chapgier A;Goldberg AD;Canaani E;Rafii S;Zheng D;Allis CD
多梳抑制复合物2（PRC 2）通过组蛋白H3（H3 K27 me3）上的赖氨酸27的三甲基化来调节谱系特化期间的基因表达。在果蝇中，polycomb结合位点是富含组蛋白变体H3.3的动态染色质区域。在这里，我们表明，在小鼠胚胎干细胞（ESCs）H3.3是需要适当的建立H3K27me3在发育调控基因的启动子。在H3.3耗尽后，这些启动子显示通过从头合成的组蛋白的沉积测量的核小体周转减少，并且PRC2占据减少。此外，我们显示H3.3依赖的PRC2与组蛋白伴侣，希拉，和希拉本地化的染色质需要H3.3的相互作用。我们的数据证明了H3.3在维持ESC中染色质景观方面的重要性，这对于分化期间的适当基因调控很重要。此外，我们的研究结果支持新出现的概念，即H3.3在不同的基因组位置具有多种功能，这些功能并不总是与“活跃”的染色质状态相关。
Polycomb repressive complex 2 (PRC2) regulates gene expression during lineage specification through trimethylation of lysine 27 on histone H3 (H3K27me3). In Drosophila, polycomb binding sites are dynamic chromatin regions enriched with the histone variant H3.3. Here we show that in mouse embryonic stem cells (ESCs) H3.3 is required for proper establishment of H3K27me3 at the promoters of developmentally regulated genes. Upon H3.3 depletion, these promoters show reduced nucleosome turnover measured by deposition of de novo synthesized histones, and reduced PRC2 occupancy. Further, we show H3.3-dependent interaction of PRC2 with the histone chaperone, Hira, and that Hira localization to chromatin requires H3.3. Our data demonstrate the importance of H3.3 in maintaining a chromatin landscape in ESCs that is important for proper gene regulation during differentiation. Moreover, our findings support the emerging notion that H3.3 has multiple functions in distinct genomic locations that are not always correlated with an “active” chromatin state.
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影响因子：
23.9
作者：
Brookes, Emily;de Santiago, Ines;Hebenstreit, Daniel;Morris, Kelly J.;Carroll, Tom;Xie, Sheila Q.;Stock, Julie K.;Heidemann, Martin;Eick, Dirk;Nozaki, Naohito;Kimura, Hiroshi;Ragoussis, Jiannis;Teichmann, Sarah A.;Pombo, Ana
通讯作者：
Pombo, Ana
影响因子：
64.5
作者：
Goldberg AD;Banaszynski LA;Noh KM;Lewis PW;Elsaesser SJ;Stadler S;Dewell S;Law M;Guo X;Li X;Wen D;Chapgier A;DeKelver RC;Miller JC;Lee YL;Boydston EA;Holmes MC;Gregory PD;Greally JM;Rafii S;Yang C;Scambler PJ;Garrick D;Gibbons RJ;Higgs DR;Cristea IM;Urnov FD;Zheng D;Allis CD
通讯作者：
Allis CD
变体组蛋白 H3.3 对颅神经嵴外间质潜能的重要作用。
影响因子：
4.5
作者：
Cox SG;Kim H;Garnett AT;Medeiros DM;An W;Crump JG
通讯作者：
Crump JG
影响因子：
10.5
作者：
Li, Gang;Margueron, Raphael;Reinberg, Danny
通讯作者：
Reinberg, Danny
影响因子：
3.9
作者：
Bush KM;Yuen BT;Barrilleaux BL;Riggs JW;O'Geen H;Cotterman RF;Knoepfler PS
通讯作者：
Knoepfler PS