Journal
EMBO JOURNAL
Volume 37, Issue 8, Pages -Publisher
WILEY
DOI: 10.15252/embj.201797174
Keywords
embryogenesis; ESC pluripotency; LncKdm2b; SRCAP; Zbtb3
Categories
Funding
- National Natural Science Foundation of China [91640203, 31530093, 91419308, 31470864, 31670886, 81472413, 81672956, 31601189, 31401098, 31520103905, 81572433, 81772646]
- Beijing Natural Science Foundation [7181006]
- Strategic Priority Research Programs of the Chinese Academy of Sciences [XDB19030203]
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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.
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