title: NF-κB forms a complex with the chromatin remodeler BRG1 to regulate Schwann cell differentiation.
abstract: In the developing peripheral nervous system, axon-derived signals stimulate Schwann cells to undergo a global genetic reprogramming involving the cessation of cellular division and the upregulation of myelin genes. How such a comprehensive change in gene transcription is regulated is poorly understood. Here we report that BRG1/SMARCA4, the central helicase of the mammalian SWI/SNF-related chromatin remodeling complex, is required for Schwann cells to differentiate and form myelin, both in vitro and in vivo, in the mouse. BRG1 was highly activated in Schwann cells at early stages of myelination, and loss of the enzyme inhibited their differentiation and completely prevented myelin formation. Furthermore, we identify NF-κB as a key transcription factor that associates with the BRG1 complex in response to neuregulin 1 type III. During myelination, BRG1 was activated through the formation of a complex with NF-κB, and both proteins bound to the promoter region of Sox10, an inducer of myelination. These findings delineate a novel mechanism whereby axonal signals promote myelination through the remodeling of chromatin structure.
authors: Department Biochemistry and Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors: Allison S
authors: AS
authors: Limpert
authors: Shujun
authors: S
authors: Bai
authors: Malathi
authors: M
authors: Narayan
authors: Jiang
authors: J
authors: Wu
authors: Sung Ok
authors: SO
authors: Yoon
authors: Bruce D
authors: BD
authors: Carter
authors: Q Richard
authors: QR
authors: Lu
mesh_terms: D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000378:metabolism* / Q000502:physiology; D018920:Coculture Techniques; D004265:DNA Helicases / Q000378:metabolism* / Q000502:physiology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism* / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology
chemical_list: D002843:Chromatin; D016328:NF-kappa B; D009687:Nuclear Proteins; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases
references: Cell. 2007 Feb 23;128(4):707-19
references: 17320508
references: J Neurosci Res. 2004 Jun 1;76(5):593-8
references: 15139018
references: Neuron. 2007 Oct 4;56(1):94-108
references: 17920018
references: Oncogene. 2006 Aug 28;25(38):5220-7
references: 16936740
references: Science. 1993 Mar 26;259(5103):1912-5
references: 8096091
references: Nat Neurosci. 2009 Jul;12(7):839-47
references: 19525946
references: Development. 2007 Sep;134(18):3271-81
references: 17699610
references: Nat Neurosci. 2011 Apr;14(4):429-36
references: 21423190
references: Mol Cell Biol. 2005 May;25(10):3997-4009
references: 15870273
references: Glia. 2008 Nov 1;56(14):1541-51
references: 18803322
references: J Biol Chem. 2001 Jan 26;276(4):2841-51
references: 11042203
references: Prog Biophys Mol Biol. 2010 Jun-Jul;102(2-3):122-8
references: 20493208
references: J Neurosci. 2002 Dec 1;22(23):10333-45
references: 12451133
references: Mol Cell Biol. 2007 May;27(9):3521-9
references: 17325040
references: EMBO Rep. 2006 Jan;7(1):52-8
references: 16311519
references: Nat Rev Genet. 2006 Jun;7(6):461-73
references: 16708073
references: Nat Neurosci. 2010 Dec;13(12):1472-80
references: 21057508
references: J Cell Biol. 2010 May 17;189(4):701-12
references: 20457761
references: Nat Genet. 2001 Feb;27(2):187-90
references: 11175787
references: J Exp Med. 2003 Dec 15;198(12):1937-49
references: 14676303
references: EMBO J. 2002 Sep 2;21(17):4612-20
references: 12198163
references: Cell Res. 2011 Mar;21(3):381-95
references: 21321607
references: Neuron. 2005 Sep 1;47(5):681-94
references: 16129398
references: Mol Cell Biol. 2000 May;20(9):3198-209
references: 10757804
references: Genes Dev. 2005 Dec 1;19(23):2849-61
references: 16287714
references: Genes Dev. 2001 Jan 1;15(1):66-78
references: 11156606
references: J Biol Chem. 2010 May 28;285(22):16614-22
references: 20360002
references: J Cell Biol. 2004 Feb 2;164(3):385-94
references: 14757751
references: Cell. 1998 Nov 25;95(5):625-36
references: 9845365
references: Science. 2009 Jan 30;323(5914):651-4
references: 19179536
references: Eur J Neurosci. 1993 Sep 1;5(9):1136-44
references: 7506619
references: Dev Cell. 2012 Jul 17;23(1):193-201
references: 22814607
references: J Neurosci. 2000 Jun 15;20(12):4627-34
references: 10844032
references: J Neurosci. 1998 Jan 1;18(1):237-50
references: 9412504
references: Hum Mol Genet. 1999 Jul;8(7):1245-51
references: 10369870
references: Mol Cell Biol. 1997 Oct;17(10):5976-86
references: 9315656
references: EMBO J. 2006 Feb 8;25(3):490-501
references: 16424906
references: Genes Dev. 2002 Oct 1;16(19):2509-17
references: 12368262
references: Nat Neurosci. 2003 Feb;6(2):161-7
references: 12514737
references: Glia. 2011 Jul;59(7):1022-32
references: 21491499
references: Development. 2004 Nov;131(22):5599-612
references: 15496445
references: Mol Cell Biol. 2004 Jan;24(1):362-76
references: 14673169
references: Cell Res. 2011 Mar;21(3):396-420
references: 21358755
references: Genes Dev. 1996 Jul 15;10(14):1751-62
references: 8698235
references: J Neurosci. 2008 Apr 2;28(14):3738-46
references: 18385332
references: Nat Neurosci. 2011 Apr;14(4):437-41
references: 21423191