Jmjd2b/Kdm4b 和 Jmjd2c/Kdm4c 在小鼠胚胎干细胞特性中的独特和组合功能。
Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity.
机构信息
Dana Farber Boston Children's Hospital Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA 02115, USA.
Department of Stem Cell and Regenerative Biology, Harvard University and Harvard Medical School, 7 Divinity Avenue, Cambridge, MA 02138.
出版信息
Mol Cell. 2014 Jan 9;53(1):32-48. doi: 10.1016/j.molcel.2013.11.011. Epub 2013 Dec 19.
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 mouse ESC identity. In-depth analyses demonstrate that the closely related HDMs Jmjd2b and Jmjd2c are necessary for self-renewal of ESCs and induced pluripotent stem cell generation. Genome-wide occupancy studies reveal that 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 an aspect of multilayered transcriptional control.
胚胎干细胞 (ESC) 的自我更新和多能性是由多个在多个水平上运作的调控途径建立的。组蛋白去甲基酶 (HDMs) 在这些程序中的作用尚未完全确定。我们进行了功能 RNAi 筛选以鉴定 HDMs，并鉴定了五个对小鼠 ESC 特性至关重要的潜在 HDMs。深入分析表明，密切相关的 HDMs Jmjd2b 和 Jmjd2c 对于 ESC 的自我更新和诱导多能干细胞的产生是必需的。全基因组占据研究表明，Jmjd2b 独特、Jmjd2c 独特和 Jmjd2b-Jmjd2c 常见的靶位点分别属于功能上可分离的核心、多梳抑制复合物 (PRC) 和 Myc 调节模块。Jmjd2b 和 Nanog 通过相互连接的调节环起作用，而 Jmjd2c 则协助 PRC2 进行转录抑制。因此，同一亚类的两个 HDMs 在控制 ESC 状态方面表现出不同和组合的功能。这种 HDM 功能的复杂性揭示了转录控制的多层方面。
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