Open AccessCtbp2 Modulates NuRD‐Mediated Deacetylation of H3K27 and Facilitates PRC2‐Mediated H3K27me3 in Active Embryonic Stem Cell Genes During Exit from Pluripotency
Author(s) -
Kim Tae Wan,
Kang ByungHee,
Jang Hyonchol,
Kwak Sojung,
Shin Jihoon,
Kim Hyunsoo,
Lee SangEun,
Lee SoonMin,
Lee JongHyuk,
Kim JaeHwan,
Kim SeonYoung,
Cho EunJung,
Kim Ju Han,
Park Keun Soo,
Che JeongHwan,
Han Dong Wook,
Kang Min Jueng,
Yi Eugene C.,
Youn HongDuk
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2046
Subject(s) - biology , prc2 , embryonic stem cell , microbiology and biotechnology , epigenetics , gene silencing , histone , cellular differentiation , stem cell , genetics , gene , ezh2
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. S tem C ells 2015;33:2442–2455