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

First Author  Feng W Year  2013
Journal  Cell Stem Cell Volume  13
Issue  1 Pages  62-72
PubMed ID  23827709 Mgi Jnum  J:199367
Mgi Id  MGI:5502471 Doi  10.1016/j.stem.2013.05.002
Citation  Feng W, et al. (2013) The Chromatin Remodeler CHD7 Regulates Adult Neurogenesis via Activation of SoxC Transcription Factors. Cell Stem Cell 13(1):62-72
abstractText  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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