Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity

Das, P. P., Shao, Z., Beyaz, S., Apostolou, E., Pinello, L., Angeles, A. L., O'Brien, K., Atsma, J. M., Fujiwara, Y., Nguyen, M., Ljuboja, D., Guo, G., Woo, A., Yuan, G. C., Onder, T., Daley, G., Hochedlinger, K., Kim, J., Orkin, S. H. (January 2014) Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity. Mol Cell, 53 (1). pp. 32-48. ISSN 1097-4164 (Electronic)1097-2765 (Linking)

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.

Item Type:	Paper
Uncontrolled Keywords:	Animals Cell Line Embryonic Stem Cells/cytology/*enzymology Genome-Wide Association Study Homeodomain Proteins/genetics/metabolism Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism Mice Nanog Homeobox Protein Pluripotent Stem Cells/cytology/*enzymology Polycomb Repressive Complex 2/genetics/metabolism Proto-Oncogene Proteins c-myc/genetics/metabolism Transcription, Genetic/*physiology
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > homeodomain protein organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:	Beyaz, Semir
Communities:	CSHL labs > Beyaz lab
Depositing User:	Matt Covey
Date:	9 January 2014
Date Deposited:	01 Feb 2018 21:56
Last Modified:	01 Feb 2018 21:56
PMCID:	PMC3919500
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/36050

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