| Literature DB >> 24361252 |
Partha Pratim Das1, Zhen Shao1, Semir Beyaz1, Eftychia Apostolou2,3, Luca Pinello4, Alejandro De Los Angeles1, Kassandra O'Brien1, Jennifer Marino Atsma1, Yuko Fujiwara1, Minh Nguyen1, Damir Ljuboja1, Guoji Guo1, Andrew Woo5, Guo-Cheng Yuan4, Tamer Onder1,6, George Daley1,7,2, Konrad Hochedlinger7,2,3, Jonghwan Kim1, Stuart H Orkin1,7.
Abstract
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.Entities:
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Year: 2013 PMID： 24361252 PMCID： PMC3919500 DOI： 10.1016/j.molcel.2013.11.011
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970