LncKdm2b controls self-renewal of embryonic stem cells via activating expression of transcription factor Zbtb3
LncKdm2b controls self-renewal of embryonic stem cells via activating expression of transcription factor Zbtb3
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LncKdm2b通过激活转录因子Zbtb3的表达来控制胚胎干细胞的自我更新
DOI：
10.15252/embj.201797174
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发表时间：
2018-04-13
期刊：
影响因子：
11.4
通讯作者：
Fan, Zusen
中科院分区：
文献类型：
--
作者：
Ye, Buqing;Liu, Benyu;Fan, Zusen
发散型长链非编码rna （Divergent long noncoding rna, lncRNAs）是小鼠和人类基因组中一种主要的lncRNA生物类型。不同lncrna的生物学和分子功能在很大程度上仍然未知。在这里，我们发现lncKdm2b是Kdm2b基因的一个分化lncRNA，在5种哺乳动物物种中保守，并在胚胎干细胞（ESCs）和早期胚胎中高度表达。LncKdm2b敲除会损害ESC自我更新并导致早期胚胎死亡。LncKdm2b可以通过促进snf2相关的CREBBP激活蛋白（SRCAP）复合物在反式中的组装和atp酶活性来激活Zbtb3。Zbtb3以纳米依赖的方式增强ESC的自我更新。最后，Zbtb3缺乏损害ESC自我更新和早期胚胎发育。因此，我们的研究结果表明，lncrna可能代表了ESC自我更新和早期胚胎发生调控的另一层。
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.