Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination

Danyang He, Corentine Marie, Chuntao Zhao, Bongwoo Kim, Jincheng Wang, Yaqi Deng, Adrien Clavairoly, Magali Frah, Haibo Wang, Xuelian He, Hatem Hmidan, Blaise V. Jones, David Witte, Bernard Zalc, Xin Zhou, Daniel I. Choo, Donna M. Martin, Carlos Parras, Q. Richard Lu

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Mutations in CHD7, encoding ATP-dependent chromodomain helicase DNA-binding protein 7, in CHARGE syndrome lead to multiple congenital anomalies, including craniofacial malformations, neurological dysfunction and growth delay. Mechanisms underlying the CNS phenotypes remain poorly understood. We found that Chd7 is a direct transcriptional target of oligodendrogenesis-promoting factors Olig2 and Smarca4/Brg1 and is required for proper onset of CNS myelination and remyelination. Genome-occupancy analyses in mice, coupled with transcriptome profiling, revealed that Chd7 interacted with Sox10 and targeted the enhancers of key myelinogenic genes. These analyses identified previously unknown Chd7 targets, including bone formation regulators Osterix (also known as Sp7) and Creb3l2, which are also critical for oligodendrocyte maturation. Thus, Chd7 coordinates with Sox10 to regulate the initiation of myelinogenesis and acts as a molecular nexus of regulatory networks that account for the development of a seemingly diverse array of lineages, including oligodendrocytes and osteoblasts, pointing to previously uncharacterized Chd7 functions in white matter pathogenesis in CHARGE syndrome.

Original languageEnglish (US)
Pages (from-to)678-689
Number of pages12
JournalNature neuroscience
Volume19
Issue number5
DOIs
StatePublished - May 1 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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    He, D., Marie, C., Zhao, C., Kim, B., Wang, J., Deng, Y., Clavairoly, A., Frah, M., Wang, H., He, X., Hmidan, H., Jones, B. V., Witte, D., Zalc, B., Zhou, X., Choo, D. I., Martin, D. M., Parras, C., & Lu, Q. R. (2016). Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination. Nature neuroscience, 19(5), 678-689. https://doi.org/10.1038/nn.4258