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

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 thatlncKdm2b, a divergent lncRNA forKdm2bgene, is conserved among five mammalian species and highly expressed in embryonic stem cells (ESCs) and early embryos.LncKdm2bknockout impairs ESC self-renewal and causes early embryonic lethality.LncKdm2bcan activate Zbtb3 by promoting the assembly and ATPase activity of Snf2-related CREBBP activator protein (SRCAP) complex intransZbtb3 potentiates the ESC self-renewal in a Nanog-dependent manner. Finally,Zbtb3deficiency 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.