Ctbp2 Modulates NuRD-Mediated Deacetylation of H3K27 and Facilitates PRC2-Mediated H3K27me3 in Active Embryonic Stem Cell Genes During Exit from Pluripotency. (26th May 2015)

• Record Type: Journal Article
• Authors: Kim, Tae Wan; Kang, Byung-Hee; Jang, Hyonchol; Kwak, Sojung; Shin, Jihoon; Kim, Hyunsoo; Lee, Sang-Eun; Lee, Soon-Min; Lee, Jong-Hyuk; Kim, Jae-Hwan; Kim, Seon-Young; Cho, Eun-Jung; Kim, Ju Han; Park, Keun Soo; Che, Jeong-Hwan; Han, Dong Wook; Kang, Min Jueng; Yi, Eugene C.; Youn, Hong-Duk
• Is Part Of: Stem cells. Volume 33:Number 8(2015:Aug.)
• Page Start: 2442
• Page End: 2455
• Publication Date: 2015-05-26
• Subjects: Embryonic stem cells -- C-terminal binding protein -- Exit from pluripotency -- Core transcription factor -- Nucleosome remodeling and deacetylation complex -- Polycomb repressive complex 2 -- H3K27 acetylation and trimethylation -- Active embryonic stem cell genes; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2046
• Languages: English
• ISSNs: 1066-5099

Abstract

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 Abstract : 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.