title: Genome-wide analysis of EGR2/SOX10 binding in myelinating peripheral nerve.
abstract: Myelin is essential for the rapidity of saltatory nerve conduction, and also provides trophic support for axons to prevent axonal degeneration. Two critical determinants of myelination are SOX10 and EGR2/KROX20. SOX10 is required for specification of Schwann cells from neural crest, and is required at every stage of Schwann cell development. Egr2/Krox20 expression is activated by axonal signals in myelinating Schwann cells, and is required for cell cycle arrest and myelin formation. To elucidate the integrated function of these two transcription factors during peripheral nerve myelination, we performed in vivo ChIP-Seq analysis of myelinating peripheral nerve. Integration of these binding data with loss-of-function array data identified a range of genes regulated by these factors. In addition, although SOX10 itself regulates Egr2/Krox20 expression, leading to coordinate activation of several major myelin genes by the two factors, there is a large subset of genes that are activated independent of EGR2. Finally, the results identify a set of SOX10-dependent genes that are expressed in early Schwann cell development, but become subsequently repressed by EGR2/KROX20.
authors.affiliation: Waisman Center, University of Wisconsin, Madison, WI, USA.
authors.forename: Rajini
authors.initials: R
authors.lastname: Srinivasan
authors.forename: Guannan
authors.initials: G
authors.lastname: Sun
authors.forename: Sunduz
authors.initials: S
authors.lastname: Keles
authors.forename: Erin A
authors.initials: EA
authors.lastname: Jones
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Jang
authors.forename: Courtney
authors.initials: C
authors.lastname: Krueger
authors.forename: John J
authors.initials: JJ
authors.lastname: Moran
authors.forename: John
authors.initials: J
authors.lastname: Svaren
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D051767:Early Growth Response Protein 2 / Q000378:metabolism*; D005786:Gene Expression Regulation; D016678:Genome; D051379:Mice; D009186:Myelin Sheath / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055757:SOXE Transcription Factors / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism* / Q000502:physiology
chemical_list: D051767:Early Growth Response Protein 2; D055757:SOXE Transcription Factors