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EMBO J. 2018 Apr 13;37(8). pii: e97174. doi: 10.15252/embj.201797174. Epub 2018 Mar 13.

LncKdm2b controls self-renewal of embryonic stem cells via activating expression of transcription factor Zbtb3.

Ye B1, Liu B1,2, Yang L1,2, Zhu X3,4, Zhang D4, Wu W2,4, Zhu P1, Wang Y1, Wang S1, Xia P1, Du Y1, Meng S3,4, Huang G1,2, Wu J1,2, Chen R5, Tian Y6,4, Fan Z7,2.

Author information

1
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
2
University of Chinese Academy of Sciences, Beijing, China.
3
Laboratory Animal Center, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
4
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
5
Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China crs@sun5.ibp.ac.cn ytian@ibp.ac.cn fanz@moon.ibp.ac.cn.
6
University of Chinese Academy of Sciences, Beijing, China crs@sun5.ibp.ac.cn ytian@ibp.ac.cn fanz@moon.ibp.ac.cn.
7
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China crs@sun5.ibp.ac.cn ytian@ibp.ac.cn fanz@moon.ibp.ac.cn.

Abstract

Divergent long noncoding RNAs (lncRNAs) represent a major lncRNA biotype in mouse and human genomes. The biological and molecular functions of the divergent lncRNAs remain largely unknown. Here, we show that lncKdm2b, a divergent lncRNA for Kdm2b gene, is conserved among five mammalian species and highly expressed in embryonic stem cells (ESCs) and early embryos. LncKdm2b knockout impairs ESC self-renewal and causes early embryonic lethality. LncKdm2b can activate Zbtb3 by promoting the assembly and ATPase activity of Snf2-related CREBBP activator protein (SRCAP) complex in trans Zbtb3 potentiates the ESC self-renewal in a Nanog-dependent manner. Finally, Zbtb3 deficiency impairs the ESC self-renewal and early embryonic development. Therefore, our findings reveal that lncRNAs may represent an additional layer of the regulation of ESC self-renewal and early embryogenesis.

KEYWORDS:

LncKdm2b ; SRCAP ; ESC pluripotency; Zbtb3; embryogenesis

PMID:
29535137
PMCID:
PMC5897780
DOI:
10.15252/embj.201797174
[Indexed for MEDLINE]
Free PMC Article

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