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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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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
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author 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
author_facet 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
author_sort Chai, MuhChyi
collection PubMed
description 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.
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spelling pubmed-58309292018-07-15 Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors 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 Genes Dev Research Paper 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. Cold Spring Harbor Laboratory Press 2018-01-15 /pmc/articles/PMC5830929/ /pubmed/29440260 http://dx.doi.org/10.1101/gad.301887.117 Text en © 2018 Chai et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
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
Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors
title Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors
title_full Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors
title_fullStr Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors
title_full_unstemmed Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors
title_short Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors
title_sort chromatin remodeler chd7 regulates the stem cell identity of human neural progenitors
topic Research Paper
url 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
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