Chromatin-remodeling factor Brg1 is required for Schwann cell differentiation and myelination.
Schwann cells produce myelin sheaths and thereby permit rapid saltatory conductance in the vertebrate peripheral nervous system. Their stepwise differentiation from neural crest cells is driven by a defined set of transcription factors. How this is linked to chromatin changes is not well understood. Here we show that the glial transcription factor Sox10 functions in Schwann cells by recruiting Brg1-containing chromatin-remodeling complexes via Baf60a to regulatory regions of Oct6 and Krox20 genes. It thereby stimulates expression of these transcriptional regulators that then cooperate with Sox10 to convert immature into myelinating Schwann cells. The functional interaction between Sox10 and Brg1 is evident from gain- and loss-of-function studies, similar neuropathies in the corresponding mouse mutants, and an aggravated neuropathy in compound mutants. Our results demonstrate that the transcription factor-mediated recruitment of the chromatin-remodeling machinery to specific genomic loci is an essential driving force for Schwann cell differentiation and myelination.
Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg, Erlangen, Germany.
Matthias
M
Weider
Melanie
M
Küspert
Melanie
M
Bischof
Michael R
MR
Vogl
Julia
J
Hornig
Kristina
K
Loy
Thomas
T
Kosian
Jana
J
Müller
Simone
S
Hillgärtner
Ernst R
ER
Tamm
Daniel
D
Metzger
Michael
M
Wegner
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002645:Chickens; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004265:DNA Helicases / Q000235:genetics / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012583:Schwann Cells / Q000166:cytology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D009687:Nuclear Proteins; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; C527924:Sox10 protein, mouse; D014157:Transcription Factors; C084108:SMARCA4 protein, human; C513194:Smarca4 protein, mouse; D004265:DNA Helicases