Regulation of neuronal commitment in mouse embryonic stem cells by the Reno1/Bahcc1 locus.
Hadas HezroniRotem Ben-Tov PerryNoa GilNeta DeganiIgor UlitskyPublished in: EMBO reports (2020)
Mammalian genomes encode thousands of long noncoding RNAs (lncRNAs), yet the biological functions of most of them remain unknown. A particularly rich repertoire of lncRNAs found in mammalian brain and in the early embryo. We used RNA-seq and computational analysis to prioritize lncRNAs that may regulate commitment of pluripotent cells to a neuronal fate and perturbed their expression prior to neuronal differentiation. Knockdown by RNAi of two highly conserved and well-expressed lncRNAs, Reno1 (2810410L24Rik) and lnc-Nr2f1, decreased the expression of neuronal markers and led to massive changes in gene expression in the differentiated cells. We further show that the Reno1 locus forms increasing spatial contacts during neurogenesis with its adjacent protein-coding gene Bahcc1. Loss of either Reno1 or Bahcc1 leads to an early arrest in neuronal commitment, failure to induce a neuronal gene expression program, and to global reduction in chromatin accessibility at regions that are marked by the H3K4me3 chromatin mark at the onset of differentiation. Reno1 and Bahcc1 thus form a previously uncharacterized circuit required for the early steps of neuronal commitment.
Keyphrases
- gene expression
- cerebral ischemia
- rna seq
- induced apoptosis
- poor prognosis
- dna methylation
- genome wide
- single cell
- genome wide identification
- subarachnoid hemorrhage
- dna damage
- quality improvement
- blood brain barrier
- genome wide analysis
- signaling pathway
- cell cycle arrest
- copy number
- pregnant women
- cell cycle
- pregnancy outcomes
- functional connectivity