title: The chromatin remodeler CHD7 regulates adult neurogenesis via activation of SoxC transcription factors.
abstract: 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.
authors.affiliation: Helmholtz Young Investigator Group-Normal and Neoplastic CNS Stem Cells, German Cancer Research Center DKFZ, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Weijun
authors.initials: W
authors.lastname: Feng
authors.forename: Muhammad Amir
authors.initials: MA
authors.lastname: Khan
authors.forename: Pablo
authors.initials: P
authors.lastname: Bellvis
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhu
authors.forename: Olga
authors.initials: O
authors.lastname: Bernhardt
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Hai-Kun
authors.initials: HK
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D004268:DNA-Binding Proteins / Q000502:physiology*; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007124:Immunoenzyme Techniques; D051379:Mice; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: C507367:Chd7 protein, mouse; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; C489990:Sox4 protein, mouse