title: Chd7 cooperates with Sox10 and regulates the onset of CNS myelination and remyelination.
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.
authors.affiliation: Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.|Integrative Biology Graduate Training Program, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Danyang
authors.initials: D
authors.lastname: He
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Inserm U1127, CNRS UMR 7225, GH Pitié-Salpêtrière, Institut du Cerveau et de la Moelle Épinière, ICM, Paris, France.
authors.forename: Corentine
authors.initials: C
authors.lastname: Marie
authors.affiliation: Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Chuntao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Integrative Biology Graduate Training Program, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Bongwoo
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Inserm U1127, CNRS UMR 7225, GH Pitié-Salpêtrière, Institut du Cerveau et de la Moelle Épinière, ICM, Paris, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Clavairoly
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Inserm U1127, CNRS UMR 7225, GH Pitié-Salpêtrière, Institut du Cerveau et de la Moelle Épinière, ICM, Paris, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Frah
authors.affiliation: Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Xuelian
authors.initials: X
authors.lastname: He
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Inserm U1127, CNRS UMR 7225, GH Pitié-Salpêtrière, Institut du Cerveau et de la Moelle Épinière, ICM, Paris, France.
authors.forename: Hatem
authors.initials: H
authors.lastname: Hmidan
authors.affiliation: Division of Radiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Blaise V
authors.initials: BV
authors.lastname: Jones
authors.affiliation: Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: David
authors.initials: D
authors.lastname: Witte
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Inserm U1127, CNRS UMR 7225, GH Pitié-Salpêtrière, Institut du Cerveau et de la Moelle Épinière, ICM, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zalc
authors.affiliation: Department of Genetics, The University of Texas Maryland Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Division of Pediatric Otolaryngology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Choo
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.|Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Martin
authors.affiliation: Sorbonne Universités, UPMC University Paris 06, Inserm U1127, CNRS UMR 7225, GH Pitié-Salpêtrière, Institut du Cerveau et de la Moelle Épinière, ICM, Paris, France.
authors.forename: Carlos
authors.initials: C
authors.lastname: Parras
authors.affiliation: Department of Pediatrics, Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.|Integrative Biology Graduate Training Program, University of Texas Southwestern Medical Center, Dallas, Texas, USA.|Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Q Richard
authors.initials: QR
authors.lastname: Lu
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D050976:Basic-Leucine Zipper Transcription Factors; D058747:CHARGE Syndrome / Q000503:physiopathology*; D004265:DNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009186:Myelin Sheath / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D055495:Neurogenesis / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism / Q000502:physiology; D055757:SOXE Transcription Factors / Q000378:metabolism / Q000502:physiology*; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D055757:SOXE Transcription Factors; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors; C507367:Chd7 protein, mouse; C544811:Creb3l2 protein, mouse; C512773:Olig2 protein, mouse; C527924:Sox10 protein, mouse; C479466:Sp7 protein, mouse; C513194:Smarca4 protein, mouse