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Publication : Regulation of neuronal commitment in mouse embryonic stem cells by the Reno1/Bahcc1 locus.

First Author  Hezroni H Year  2020
Journal  EMBO Rep Volume  21
Issue  11 Pages  e51264
PubMed ID  32969152 Mgi Jnum  J:301382
Mgi Id  MGI:6505167 Doi  10.15252/embr.202051264
Citation  Hezroni H, et al. (2020) Regulation of neuronal commitment in mouse embryonic stem cells by the Reno1/Bahcc1 locus. EMBO Rep 21(11):e51264
abstractText  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.
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