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

Buqing Ye; Benyu Liu; Liuliu Yang; Xiaoxiao Zhu; Dongdong Zhang; Wei Wu; Pingping Zhu; Yanying Wang; Shuo Wang; Pengyan Xia; Ying Du; Shu Meng; Guanling Huang; Jiayi Wu; Runsheng Chen; Yong Tian; Zusen Fan

doi:10.15252/embj.201797174

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

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

Authors

Buqing Ye¹, Benyu Liu^{1

2}, Liuliu Yang^{1

2}, Xiaoxiao Zhu^{3

4}, Dongdong Zhang⁴, Wei Wu^{2

4}, Pingping Zhu¹, Yanying Wang¹, Shuo Wang¹, Pengyan Xia¹, Ying Du¹, Shu Meng^{3

4}, Guanling Huang^{1

2}, Jiayi Wu^{1

2}, Runsheng Chen⁵, Yong Tian^{6

4}, Zusen Fan^{7

2}

Affiliations

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
DNA-Binding Proteins / genetics*
Embryonic Development
Embryonic Stem Cells / metabolism*
Humans
Mice, Knockout
RNA, Long Noncoding / genetics*

Substances

DNA-Binding Proteins
RNA, Long Noncoding
ZBTB3 protein, human