Long non-coding RNA LncKdm2b regulates cortical neuronal differentiation by cis-activating Kdm2b

Long non-coding RNA LncKdm2b regulates cortical neuronal differentiation by cis-activating Kdm2b
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长非编码RNA LncKdm2b通过顺式激活Kdm2b调节皮质神经元分化

DOI:
10.1007/s13238-019-0650-z
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发表时间:
2018-11
期刊:
影响因子:
21.1
通讯作者:
Yan Zhou
Yan Zhou
中科院分区:
生物学1区
文献类型:
--
作者:
Wei Li;Wenchen Shen;Bo Zhang;Kuan Tian;Yamu Li;Lili Mu;Zhiyuan Luo;Xiaoling Zhong;Xudong Wu;Ying Liu;Yan Zhou

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大脑皮层神经发生的时空控制机制在很大程度上是难以捉摸的。长链非编码RNA(lncRNA)已成为细胞命运的重要调控因子。在这里,我们发现LncKdm 2b(也称为Kancr),从Kdm 2b的双向启动子发散转录的lncRNA,在皮层投射神经元的早期分化过程中瞬时表达。有趣的是,Kdm2b的转录受LncKdm2b顺式正调控,LncKdm2b具有内在激活功能,并通过与hnRNPAB结合促进Kdm2b启动子处的容许染色质环境。谱系追踪实验和表型分析表明LncKdm 2b和Kdm 2b在皮质投射神经元的正常分化和迁移中起关键作用。这些观察揭示了一个lncRNA依赖的机制,在调节皮层神经元分化。
The mechanisms underlying spatial and temporal control of cortical neurogenesis of the brain are largely elusive. Long non-coding RNAs (lncRNAs) have emerged as essential cell fate regulators. Here we found LncKdm2b (also known as Kancr), a lncRNA divergently transcribed from a bidirectional promoter of Kdm2b, is transiently expressed during early differentiation of cortical projection neurons. Interestingly, Kdm2b’s transcription is positively regulated in cis by LncKdm2b, which has intrinsic-activating function and facilitates a permissive chromatin environment at the Kdm2b’s promoter by associating with hnRNPAB. Lineage tracing experiments and phenotypic analyses indicated LncKdm2b and Kdm2b are crucial in proper differentiation and migration of cortical projection neurons. These observations unveiled a lncRNA-dependent machinery in regulating cortical neuronal differentiation.
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DOI: 10.3389/fncir.2017.00076
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