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Title 

Ctbp2 modulates NuRD-mediated deacetylation of H3K27 and facilitates PRC2-mediated H3K27me3 in active embryonic stem cell genes during exit from pluripotency

Authors 

T W KimB H KangH JangS KwakJ ShinH KimS E LeeS M LeeJ H LeeJ H KimSeon-Young KimE J ChoK S ParkJ H CheD W HanM J KangE C YiH D Youn

Publisher 

Wiley-Blackwell

Issue Date 

2015

Citation 

Stem Cells, vol. 33, no. 8, pp. 2442-2455

Keywords 

Active embryonic stem cell genesC-terminal binding proteinCore transcription factorEmbryonic stem cellsExit from pluripotencyH3K27 acetylation and trimethylationNucleosome remodeling and deacetylation complexPolycomb repressive complex 2

Abstract 

For cells to exit from pluripotency and commit to a lineage, the circuitry of a core transcription factor (CTF) network must be extinguished in an orderly manner through epigenetic modifications. However, how this choreographed epigenetic remodeling at active embryonic stem cell (ESC) genes occurs during differentiation is poorly understood. In this study, we demonstrate that C-terminal binding protein 2 (Ctbp2) regulates nucleosome remodeling and deacetylation (NuRD)-mediated deacetylation of H3K27 and facilitates recruitment of polycomb repressive complex 2 (PRC2)-mediated H3K27me3 in active ESC genes for exit from pluripotency during differentiation. By genomewide analysis, we found that Ctbp2 resides in active ESC genes and co-occupies regions with ESC CTFs in undifferentiated ESCs. Furthermore, ablation of Ctbp2 effects inappropriate gene silencing in ESCs by sustaining high levels of H3K27ac and impeding H3K27me3 in active ESC genes, thereby sustaining ESC maintenance during differentiation. Thus, Ctbp2 preoccupies regions in active genes with the NuRD complex in undifferentiated ESCs that are directed toward H3K27me3 by PRC2 to induce stable silencing, which is pivotal for natural lineage commitment. Stem Cells 2015; 33:2442-2455 C-terminal binding protein 2 modulates the deacetylation of H3K27 with NuRD and is required for PRC2-mediated H3K27me3 in active ESC genes for exit from pluripotency during ESC differentiation.

ISSN 

1066-5099

Link 

http://dx.doi.org/10.1002/stem.2046

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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