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Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors

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 id...

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Detalles Bibliográficos
Autores principales: Chai, MuhChyi, Sanosaka, Tsukasa, Okuno, Hironobu, Zhou, Zhi, Koya, Ikuko, Banno, Satoe, Andoh-Noda, Tomoko, Tabata, Yoshikuni, Shimamura, Rieko, Hayashi, Tetsutaro, Ebisawa, Masashi, Sasagawa, Yohei, Nikaido, Itoshi, Okano, Hideyuki, Kohyama, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5830929/
https://www.ncbi.nlm.nih.gov/pubmed/29440260
http://dx.doi.org/10.1101/gad.301887.117
Descripción
Sumario: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.