Histone chaperone HIRA regulates neural progenitor cell proliferation and neurogenesis via β-catenin

The Journal of Cell Biology
Yanxin Li, Jianwei Jiao

Abstract

Histone cell cycle regulator (HIRA) is a histone chaperone and has been identified as an epigenetic regulator. Subsequent studies have provided evidence that HIRA plays key roles in embryonic development, but its function during early neurogenesis remains unknown. Here, we demonstrate that HIRA is enriched in neural progenitor cells, and HIRA knockdown reduces neural progenitor cell proliferation, increases terminal mitosis and cell cycle exit, and ultimately results in premature neuronal differentiation. Additionally, we demonstrate that HIRA enhances β-catenin expression by recruiting H3K4 trimethyltransferase Setd1A, which increases H3K4me3 levels and heightens the promoter activity of β-catenin. Significantly, overexpression of HIRA, HIRA N-terminal domain, or β-catenin can override neurogenesis abnormities caused by HIRA defects. Collectively, these data implicate that HIRA, cooperating with Setd1A, modulates β-catenin expression and then regulates neurogenesis. This finding represents a novel epigenetic mechanism underlying the histone code and has profound and lasting implications for diseases and neurobiology.

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Citations

Apr 4, 2020·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Juanmei GaoWanhua Shen
Apr 18, 2020·BMC Genomics·Juan Moriano, Cedric Boeckx
Nov 22, 2020·Cells·Marta Garcia-FornSilvia De Rubeis
May 8, 2021·Frontiers in Cell and Developmental Biology·Reuben FranklinSihem Cheloufi
Oct 15, 2021·Journal of Experimental & Clinical Cancer Research : CR·Rui WangYamei Pang

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Datasets Mentioned

BETA
AB2237

Methods Mentioned

BETA
chemical modification
PCR
immunoprecipitation
ChIP
transfection
coimmunoprecipitation
Protein Assay
Infrared Imaging

Software Mentioned

ZEN

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