Long non-coding RNA LncKdm2bregulates cortical neuronal differentiation by cis-activating Kdm2b

Abstract

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 cisby 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 LncKdm2band Kdm2bare crucial in proper differentiation and migration of cortical projection neurons. These observations unveiled a lncRNA-dependent machinery in regulating cortical neuronal differentiation.

Keywords

long non-coding RNA / neuronal differentiation / cerebral cortex / KDM2B / divergent lncRNA

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