@article{d74cbebe82bc428c83ed9bff3aadb9d3,
title = "Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors",
abstract = "Multiple congenital disorders often present complex phenotypes, but how the mutation of individual genetic factors can lead to multiple defects remains poorly understood. In the present study, we used human neuroepithelial (NE) cells and CHARGE patient-derived cells as an in vitro model system to identify the function of chromodomain helicase DNA-binding 7 (CHD7) in NE–neural crest bifurcation, thus revealing an etiological link between the central nervous system (CNS) and craniofacial anomalies observed in CHARGE syndrome. We found that CHD7 is required for epigenetic activation of superenhancers and CNS-specific enhancers, which support the maintenance of the NE and CNS lineage identities. Furthermore, we found that BRN2 and SOX21 are downstream effectors of CHD7, which shapes cellular identities by enhancing a CNS-specific cellular program and indirectly repressing non-CNS-specific cellular programs. Based on our results, CHD7, through its interactions with superenhancer elements, acts as a regulatory hub in the orchestration of the spatiotemporal dynamics of transcription factors to regulate NE and CNS lineage identities.",
keywords = "CHARGE syndrome, CHD7, ChIP-seq, Neural crest, Neural progenitors, Superenhancers",
author = "Muhchyi Chai and Tsukasa Sanosaka and Hironobu Okuno and Zhi Zhou and Ikuko Koya and Satoe Banno and Tomoko Andoh-Noda and Yoshikuni Tabata and Rieko Shimamura and Tetsutaro Hayashi and Masashi Ebisawa and Yohei Sasagawa and Itoshi Nikaido and Hideyuki Okano and Jun Kohyama",
note = "Funding Information: We thank Dr. Austin Smith (University of Cambridge) for providing AF22, Dr. Shinya Yamanaka (Kyoto University) for providing human iPSC clones (201B7 and 1210B2), and Dr. H. Miyoshi (Keio University) for the lentiviral vectors. We also thank the members of H. Okano{\textquoteright}s laboratories for helpful comments, and Dr. Douglas Sipp for proofreading the manuscript. This work was supported by the Japan Society for the Promotion of Science KAKENHI grant numbers JP16K15240 and JP26713047 to J.K. This research was also supported by research funding from Eisai Co., Ltd. (to H. Okano.), the Research Project for Practical Application of Re- generative Medicine from the Japan Agency for Medical Research and Development (AMED; to J.K.), the Research Center Network for Realization of Regenerative Medicine from the Japan Sciences and Technology Agency (JST), and AMED (to I.N. and H. Okano.). This research is partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from the Ministry of Education, Culture, Sports, Science and Technology and AMED (to I.N.). Publisher Copyright: {\textcopyright} 2018 Chai et al.",
year = "2018",
month = jan,
day = "15",
doi = "10.1101/gad.301887.117",
language = "English",
volume = "32",
pages = "165--180",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "2",
}