Long non-coding RNA LncKdm2b regulates 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 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.

Epigenetic Impacts of Early Life Stress in Fetal Alcohol Spectrum Disorders Shape the Neurodevelopmental Continuum

“…Similarly, the histone methyltransferase of polycomb repressive complex 2, EZH2, is critical for maintaining the timing and number of cells produced from progenitor cells (Pereira et al, 2010 ). Cell migration is regulated by long ncRNA (lncRNA) via cis-activation of the lysine demethylase Kdm2b , a critical factor in the migration of cortical projection neurons (Li et al, 2020 ). The histone H3K27 demethylase, lysine demethylase 6a ( Kdm6a ), is critical for appropriate synapse formation and transmission through the regulation of genes such as the neurotransmitter receptor Htr5b (Tang et al, 2017 ).…”

“…Next, the cells must migrate out of this ventricular zone to form the cortex, a process that peaks during early postnatal development (Sanai et al, 2011 ). Cell migration is mediated by gene expression events, noncoding RNA, and the removal of histone post-translational modifications (Li et al, 2020 ). Depending on location, the cells will differentiate into neurons, growing axons and dendrites, ultimately forming synapses with other cells.…”

The Roles of Long Noncoding RNAs HNF1α-AS1 and HNF4α-AS1 in Drug Metabolism and Human Diseases

“…On the other hand, trans-regulatory lncRNAs are involved in the regulation of distal genes from their transcription sites, where lncRNA FIRRE is an example [14]. However, with the progression in understanding lncRNA function, lncRNAs with both cis-and trans-regulatory functions have been identified, where the lncRNA lncKdm2b is an example [15,16].…”

A New View of Genome Organization Through RNA Directed Interactions

“…They do so by promoting long-range chromatin interactions and the bridging of distant genomic loci (Figure 1C). Type II RNAs include examples such as the lncRNAs LUNAR1 or Kancr, both involved in chromosomal looping and activation of genes near the loop anchor points (Trimarchi et al, 2014;Li et al, 2020). Additionally, some lncRNAs can potentially exhibit both types of interactions.…”