UBN1/2 of HIRA complex is responsible for recognition and deposition of H3.3 at cis-regulatory elements of genes in mouse ES cells.
UBN1/2 of HIRA complex is responsible for recognition and deposition of H3.3 at cis-regulatory elements of genes in mouse ES cells.
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HIRA 复合体的 UBN1/2 负责在小鼠 ES 细胞基因的顺式调控元件处识别和沉积 H3.3
DOI：
10.1186/s12915-018-0573-9
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发表时间：
2018-10-03
期刊：
影响因子：
5.4
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Xiong C;Wen Z;Yu J;Chen J;Liu CP;Zhang X;Chen P;Xu RM;Li G
背景：H3.3是一种古老而保守的H3变异体，在转录调控中起重要作用。HIRA复合物是由HIRA、UBN 1或UBN 2和Cabin1组成的H3.3特异性分子伴侣复合物。然而，它仍然在很大程度上是未知的HIRA复合物如何特异性地识别和存款H3.3的染色质，如promoters和enhancers.Results：在这项研究中，我们证明，UBN 1或UBN 2亚基主要负责特异性识别和直接结合H3.3的HIRA复合物。HIRA亚基可以增强UBN 1与H3.3的结合亲和力，而Cabin1亚基则不能。我们还证明了H3.3的Ala87和Gly90残基对于UBN 1的特异性识别和结合是必需的和足够的。ChIP-seq研究表明，两个独立的HIRA复合物（UBN 1-HIRA和UBN 2-HIRA）可以协同存款H3. 3到小鼠胚胎干细胞（mES）的顺式调控区域，包括活性启动子和活性增强子。重要的是，FID/AAA突变破坏了UBN 1和UBN 2的组蛋白伴侣活性，导致H3.3沉积在参与神经分化的发育基因启动子上的缺陷，并随后导致这些基因在mES细胞神经分化过程中的激活失败。总之，我们的结果提供了新的见解HIRA复合物特异性识别和沉积H3.3在发育基因的启动子和增强子的机制，其在mES细胞的神经分化中起关键作用。
Background:H3.3 is an ancient and conserved H3 variant and plays essential roles in transcriptional regulation. HIRA complex, which is composed of HIRA, UBN1 or UBN2, and Cabin1, is a H3.3 specific chaperone complex. However, it still remains largely uncharacterized how HIRA complex specifically recognizes and deposits H3.3 to the chromatin, such as promoters and enhancers.Results:In this study, we demonstrate that the UBN1 or UBN2 subunit is mainly responsible for specific recognition and direct binding of H3.3 by the HIRA complex. While the HIRA subunit can enhance the binding affinity of UBN1 toward H3.3, Cabin1 subunit cannot. We also demonstrate that both Ala87 and Gly90 residues of H3.3 are required and sufficient for the specific recognition and binding by UBN1. ChIP-seq studies reveal that two independent HIRA complexes (UBN1-HIRA and UBN2-HIRA) can cooperatively deposit H3.3 to cis-regulatory regions, including active promoters and active enhancers in mouse embryonic stem (mES) cells. Importantly, disruption of histone chaperone activities of UBN1 and UBN2 by FID/AAA mutation results in the defect of H3.3 deposition at promoters of developmental genes involved in neural differentiation, and subsequently causes the failure of activation of these genes during neural differentiation of mES cells.Conclusion:Together, our results provide novel insights into the mechanism by which the HIRA complex specifically recognizes and deposits H3.3 at promoters and enhancers of developmental genes, which plays a critical role in neural differentiation of mES cells.
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影响因子：
10.5
作者：
Drane, Pascal;Ouararhni, Khalid;Hamiche, Ali
通讯作者：
Hamiche, Ali
影响因子：
64.5
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
通讯作者：
Allis CD
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
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：
30.8
作者：
Behjati, Sam;Tarpey, Patrick S.;Presneau, Nadege;Scheipl, Susanne;Pillay, Nischalan;Van Loo, Peter;Wedge, David C.;Cooke, Susanna L.;Gundem, Gunes;Davies, Helen;Nik-Zainal, Serena;Martin, Sancha;McLaren, Stuart;Goodie, Victoria;Robinson, Ben;Butler, Adam;Teague, Jon W.;Halai, Dina;Khatri, Bhavisha;Myklebost, Ola;Baumhoer, Daniel;Jundt, Gernot;Hamoudi, Rifat;Tirabosco, Roberto;Amary, M. Fernanda;Futreal, P. Andrew;Stratton, Michael R.;Campbell, Peter J.;Flanagan, Adrienne M.
通讯作者：
Flanagan, Adrienne M.