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The chromatin remodeler CHD7 regulates adult neurogenesis via activation of SoxC transcription factors

Chromatin factors that regulate neurogenesis in the central nervous system remain to be explored. Here, we demonstrate that the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7), a protein frequently mutated in human CHARGE syndrome, is a master regulator of neurogenesis in mamm...

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Main Authors: Feng, Weijun (Author) , Khan, Muhammad Amir (Author) , Bellvís Zambrano, Pablo (Author) , Zhu, Zhe (Author) , Bernhardt, Olga (Author) , Herold-Mende, Christel (Author) , Liu, Hai-Kun (Author)
Format: Article (Journal)
Language:English
Published: 3 July 2013
In: Cell stem cell
Year: 2013, Volume: 13, Issue: 1, Pages: 62-72
ISSN:1875-9777
DOI:10.1016/j.stem.2013.05.002
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.stem.2013.05.002
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1934590913001951
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Author Notes:Weijun Feng, Muhammad Amir Khan, Pablo Bellvis, Zhe Zhu, Olga Bernhardt, Christel Herold-Mende, and Hai-Kun Liu

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520 |a Chromatin factors that regulate neurogenesis in the central nervous system remain to be explored. Here, we demonstrate that the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7), a protein frequently mutated in human CHARGE syndrome, is a master regulator of neurogenesis in mammalian brain. CHD7 is selectively expressed in actively dividing neural stem cells (NSCs) and progenitors. Genetic inactivation of CHD7 in NSCs leads to a reduction of neuronal differentiation and aberrant dendritic development of newborn neurons. Strikingly, physical exercise can rescue the CHD7 mutant phenotype in the adult hippocampal dentate gyrus. We further show that in NSCs, CHD7 stimulates the expression of Sox4 and Sox11 genes via remodeling their promoters to an open chromatin state. Our study demonstrates an essential role of CHD7 in activation of the neuronal differentiation program in NSCs, thus providing insights into epigenetic regulation of stem cell differentiation and molecular mechanism of human CHARGE syndrome. 
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