LSD1 co-repressor Rcor2 orchestrates neurogenesis in the developing mouse brain

Nature Communications
Yixuan WangXiaoqun Wang

Abstract

Epigenetic regulatory complexes play key roles in the modulation of transcriptional regulation underlying neural stem cell (NSC) proliferation and progeny specification. How specific cofactors guide histone demethylase LSD1/KDM1A complex to regulate distinct NSC-related gene activation and repression in cortical neurogenesis remains unclear. Here we demonstrate that Rcor2, a co-repressor of LSD1, is mainly expressed in the central nervous system (CNS) and plays a key role in epigenetic regulation of cortical development. Depletion of Rcor2 results in reduced NPC proliferation, neuron population, neocortex thickness and brain size. We find that Rcor2 directly targets Dlx2 and Shh, and represses their expressions in developing neocortex. In addition, inhibition of Shh signals rescues the neurogenesis defects caused by Rcor2 depletion both in vivo and in vitro. Hence, our findings suggest that co-repressor Rcor2 is critical for cortical development by repressing Shh signalling pathway in dorsal telencephalon.

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Citations

Jan 5, 2017·Proceedings of the National Academy of Sciences of the United States of America·Caitlin E MonaghanGail Mandel
Mar 21, 2018·The Biochemical Journal·Julián Esteban SáezMaría Estela Andrés
Dec 9, 2017·Pharmaceutical Patent Analyst·Hermann Am Mucke
Oct 3, 2018·Journal of Neurochemistry·Nicole AmbergSimon Hippenmeyer
Apr 2, 2019·Frontiers in Neuroscience·Ole Kristian DrangeOle A Andreassen
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Nov 2, 2019·Investigative Ophthalmology & Visual Science·Salma FerdousJohn M Nickerson
Dec 19, 2018·Oncotarget·Kathleen I Pishas, Stephen L Lessnick
Jan 9, 2021·Genome Research·Saurabh AgarwalShigeki Iwase
Jun 4, 2021·Circulation Research·Jin-Ling HuoWen Zhao
Jun 5, 2021·Journal of Biomedical Science·Dongha KimSung Hee Baek

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Datasets Mentioned

BETA
GSE75040

Methods Mentioned

BETA
PCR
ChIP-seq
RNA-seq
genotyping
Immunoprecipitation
ChIP

Software Mentioned

Photoshop
Cuffdiff
R
Illumina CASAVA pipeline
Tophat
Imaris

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