Pontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells

被引:23
作者
Boo, Kyungjin [1 ]
Bhin, Jinhyuk [2 ]
Jeon, Yoon [3 ]
Kim, Joomyung [1 ]
Shin, Hi-Jai R. [1 ]
Park, Jong-Eun [4 ]
Kim, Kyeongkyu [1 ]
Kim, Chang Rok [1 ]
Jang, Hyonchol [3 ]
Kim, In-Hoo [3 ]
Kim, V. Narry
Hwang, Daehee [2 ,5 ,6 ]
Lee, Ho [3 ]
Baek, Sung Hee [1 ]
机构
[1] Seoul Natl Univ, Creat Res Initiat Ctr Chromatin Dynam, Sch Biol Sci, Seoul 151742, South Korea
[2] POSTECH, Dept Chem Engn, Pohang 790784, South Korea
[3] Natl Canc Ctr, Res Inst, Grad Sch Canc Sci & Policy, Gyeonggi Do, South Korea
[4] Seoul Natl Univ, Inst Basic Sci, Sch Biol Sci, Seoul 151742, South Korea
[5] DGIST, Inst Basic Sci, Dept New Biol, Daegu 711873, South Korea
[6] DGIST, Inst Basic Sci, Ctr Plant Aging Res, Daegu 711873, South Korea
基金
新加坡国家研究基金会;
关键词
NONCODING RNAS; REGULATES PLURIPOTENCY; CHROMATIN; GENE; DIFFERENTIATION; TRANSCRIPTION; INTEGRATION; CIRCUITRY; REVEALS; NETWORK;
D O I
10.1038/ncomms7810
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The actions of transcription factors, chromatin modifiers and noncoding RNAs are crucial for the programming of cell states. Although the importance of various epigenetic machineries for controlling pluripotency of embryonic stem (ES) cells has been previously studied, how chromatin modifiers cooperate with specific transcription factors still remains largely elusive. Here, we find that Pontin chromatin remodelling factor plays an essential role as a coactivator for Oct4 for maintenance of pluripotency in mouse ES cells. Genome-wide analyses reveal that Pontin and Oct4 share a substantial set of target genes involved in ES cell maintenance. Intriguingly, we find that the Oct4-dependent coactivator function of Pontin extends to the transcription of large intergenic noncoding RNAs (lincRNAs) and in particular linc1253, a lineage programme repressing lincRNA, is a Pontin-dependent Oct4 target lincRNA. Together, our findings demonstrate that the Oct4-Pontin module plays critical roles in the regulation of genes involved in ES cell fate determination.
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页数:16
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