Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity.
Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity.
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DOI：
10.1016/j.molcel.2013.11.011
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发表时间：
2014-01-09
期刊：
影响因子：
16
通讯作者：
Orkin, Stuart H.
中科院分区：
文献类型：
--
作者：
Das, Partha Pratim;Shao, Zhen;Beyaz, Semir;Apostolou, Eftychia;Pinello, Luca;De Los Angeles, Alejandro;O'Brien, Kassandra;Atsma, Jennifer Marino;Fujiwara, Yuko;Minh Nguyen;Ljuboja, Damir;Guo, Guoji;Woo, Andrew;Yuan, Guo-Cheng;Onder, Tamer;Daley, George;Hochedlinger, Konrad;Kim, Jonghwan;Orkin, Stuart H.
胚胎干细胞（embryonic stem cells，ESCs）的自我更新和多能性是通过多个水平的多个调控途径实现的。组蛋白去甲基化酶（HDMs）在这些程序中的作用是不完全确定的。我们对HDM进行了功能性RNAi筛选，并确定了五种对mESC身份至关重要的潜在HDM。深入分析表明，密切相关的HDM，Jmjd 2b和Jmjd 2c，是ESC自我更新和iPSC产生所必需的。全基因组占有率研究表明，Jmjd 2b unique，Jmjd 2c unique和Jmjd 2b-Jmjd 2c共同靶位点分别属于功能上可分离的Core，Polycomb repressive complex（PRC）和Myc调控模块。Jmjd 2b和Nanog通过相互关联的调控环起作用，而Jmjd 2c协助PRC 2进行转录抑制。因此，同一子类的两个HDM在ESC状态的控制中表现出不同的和组合的功能。HDM功能的这种复杂性揭示了多层转录控制的新方面。
Self-renewal and pluripotency of embryonic stem cells (ESCs) are established by multiple regulatory pathways operating at several levels. The roles of histone demethylases (HDMs) in these programs are incompletely defined. We conducted a functional RNAi screen for HDMs and identified five potential HDMs essential for mESC identity. In depth analyses demonstrate that the closely related HDMs, Jmjd2b and Jmjd2c, are necessary for self-renewal of ESCs and iPSC generation. Genome-wide occupancy studies reveal Jmjd2b unique, Jmjd2c unique, and Jmjd2b-Jmjd2c common target sites belong to functionally separable Core, Polycomb repressive complex (PRC) and Myc regulatory modules, respectively. Jmjd2b and Nanog act through an interconnected regulatory loop, whereas Jmjd2c assists PRC2 in transcriptional repression. Thus, two HDMs of the same subclass exhibit distinct and combinatorial functions in control of the ESC state. Such complexity of HDM function reveals a novel aspect of multilayered transcriptional control.
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影响因子：
64.5
作者：
Kim J;Woo AJ;Chu J;Snow JW;Fujiwara Y;Kim CG;Cantor AB;Orkin SH
通讯作者：
Orkin SH
影响因子：
64.5
作者：
Cherry AB;Daley GQ
通讯作者：
Daley GQ
影响因子：
64.5
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
通讯作者：
Orkin, Stuart H.
影响因子：
64.5
作者：
Rahl PB;Lin CY;Seila AC;Flynn RA;McCuine S;Burge CB;Sharp PA;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Lee, TI;Jenner, RG;Young, RA
通讯作者：
Young, RA