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Brain abnormalities and intellectual disability are commonly observed in individuals with CHARGE, and neuronal differentiation is reduced in CHARGE patient-derived iPSCs and conditional knockout mouse brains. However, the mechanisms of CHD7 function in nervous system development are not well understood. In this study, we asked whether CHD7 promotes gene transcription in neural progenitor cells via changes in chromatin accessibility. We used <jats:italic>Chd7<\/jats:italic> null embryonic stem cells (ESCs) derived from <jats:italic>Chd7<\/jats:italic> mutant mouse blastocysts as a tool to investigate roles of CHD7 in neuronal and glial differentiation. Loss of <jats:italic>Chd7<\/jats:italic> significantly reduced neuronal and glial differentiation. Sholl analysis showed that loss of <jats:italic>Chd7<\/jats:italic> impaired neuronal complexity and neurite length in differentiated neurons. Genome-wide studies demonstrated that loss of <jats:italic>Chd7<\/jats:italic> leads to modified chromatin accessibility (ATAC-seq) and differential nascent expression (Bru-Seq) of neural-specific genes. These results suggest that CHD7 acts preferentially to alter chromatin accessibility of key genes during the transition of NPCs to neurons to promote differentiation. Our results form a basis for understanding the cell stage-specific roles for CHD7-mediated chromatin remodeling during cell lineage acquisition.<\/jats:p>","DOI":"10.1038\/s41598-020-74537-4","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T10:04:27Z","timestamp":1602756267000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["CHD7 promotes neural progenitor differentiation in embryonic stem cells via altered chromatin accessibility and nascent gene expression"],"prefix":"10.1038","volume":"10","author":[{"given":"Hui","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas F.","family":"Hannum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-1961","authenticated-orcid":false,"given":"Yiwen","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8331-9812","authenticated-orcid":false,"given":"Sophie F.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo D.\u2019Oliveira","family":"Albanus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjia","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Skidmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilson","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Saiakhova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Bielas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Scacheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-6695","authenticated-orcid":false,"given":"Mats","family":"Ljungman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C. 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