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

Muhchyi Chai, Tsukasa Sanosaka, Hironobu Okuno, Zhi Zhou, Ikuko Koya, Satoe Banno, Tomoko Andoh-Noda, Yoshikuni Tabata, Rieko Shimamura, Tetsutaro Hayashi, Masashi Ebisawa, Yohei Sasagawa, Itoshi Nikaido, Hideyuki Okano, Jun Kohyama

研究成果: Article

7 引用 (Scopus)

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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.

元の言語English
ページ(範囲)165-180
ページ数16
ジャーナルGenes and Development
32
発行部数2
DOI
出版物ステータスPublished - 2018 1 15

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Chai, M., Sanosaka, T., Okuno, H., Zhou, Z., Koya, I., Banno, S., Andoh-Noda, T., Tabata, Y., Shimamura, R., Hayashi, T., Ebisawa, M., Sasagawa, Y., Nikaido, I., Okano, H., & Kohyama, J. (2018). Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors. Genes and Development, 32(2), 165-180. https://doi.org/10.1101/gad.301887.117