HIRA complex presets transcriptional potential through coordinating depositions of the histone variants H3.3 and H2A.Z on the poised genes in mESCs.
HIRA complex presets transcriptional potential through coordinating depositions of the histone variants H3.3 and H2A.Z on the poised genes in mESCs.
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HIRA 复合物通过协调组蛋白变体 H3.3 和 H2A.Z 在 mESC 中平衡基因上的沉积来预设转录潜力
DOI：
10.1093/nar/gkab1221
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发表时间：
2022-01-11
影响因子：
14.9
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Yang Y;Zhang L;Xiong C;Chen J;Wang L;Wen Z;Yu J;Chen P;Xu Y;Jin J;Cai Y;Li G
组蛋白变异体与调节染色质动力学和基因组功能有关。以前，我们已经表明，组蛋白变体H3.3积极标记增强子，并与H2A.Z在启动子处合作，以使基因在小鼠胚胎干细胞（mESC）中处于平衡状态。然而，这两个重要的组蛋白变体如何在这一过程中协同发挥作用仍然是难以捉摸的。在这项研究中，我们发现，HIRA复合物，一个特定的伴侣蛋白H3.3的不同成分的消耗，导致在基因组规模的H2A.Z富集显着减少。此外，CUT&Tag数据揭示了HIRA复合物和SRCAP复合物之间的基因组共定位。体内外生化实验证实了HIRA复合物可以通过Hira亚基与SRCAP复合物相互作用。此外，我们的染色质可及性和转录分析表明，HIRA复合物有助于预设一个明确的染色质特征周围的TSS区域，以平衡基因转录。综上所述，我们的研究结果揭示了HIRA复合物在调控H3.3掺入调控区的同时，还与SRCAP协同作用，将H2A.Z存款到启动子上，共同决定了mESCs中潜在基因的转录潜力。
Histone variants have been implicated in regulating chromatin dynamics and genome functions. Previously, we have shown that histone variant H3.3 actively marks enhancers and cooperates with H2A.Z at promoters to prime the genes into a poised state in mouse embryonic stem cells (mESCs). However, how these two important histone variants collaboratively function in this process still remains elusive. In this study, we found that depletion of different components of HIRA complex, a specific chaperone of H3.3, results in significant decreases of H2A.Z enrichment at genome scale. In addition, CUT&Tag data revealed a genomic colocalization between HIRA complex and SRCAP complex. In vivo and in vitro biochemical assays verified that HIRA complex could interact with SRCAP complex through the Hira subunit. Furthermore, our chromatin accessibility and transcription analyses demonstrated that HIRA complex contributed to preset a defined chromatin feature around TSS region for poising gene transcription. In summary, our results unveiled that while regulating the H3.3 incorporation in the regulatory regions, HIRA complex also collaborates with SRCAP to deposit H2A.Z onto the promoters, which cooperatively determines the transcriptional potential of the poised genes in mESCs.
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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
影响因子：
64.8
作者：
Ayala R;Willhoft O;Aramayo RJ;Wilkinson M;McCormack EA;Ocloo L;Wigley DB;Zhang X
通讯作者：
Zhang X
影响因子：
10.5
作者：
Drane, Pascal;Ouararhni, Khalid;Hamiche, Ali
通讯作者：
Hamiche, Ali
影响因子：
4.8
作者：
Cai, Yong;Jin, Jingji;Conaway, Ronald C.
通讯作者：
Conaway, Ronald C.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK