Long Non-Coding RNA LncKdm2b Regulates Cortical Neuronal Differentiation by Cis-Activating Kdm2b

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, Kdm2bs transcription is positively regulated in cis by LncKdm2b, which has intrinsic-activating function and facilitates a permissive chromatin environment at the Kdm2bs 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. Moreover, KDM2B exerts its role relying on its leucine-rich repeats (LRR) but independent of its PRC1-related function. These observations unveiled a lncRNA-dependent machinery in regulating cortical neuronal differentiation.