NF-κB Forms a Complex with the Chromatin Remodeler BRG1 to Regulate Schwann Cell Differentiation

Overview

Journal J Neurosci

Specialty Neurology

Date 2013 Feb 9

PMID 23392668

Citations 32

Authors

Allison S Limpert

Shujun Bai

Malathi Narayan

Jiang Wu

Sung Ok Yoon

Bruce D Carter

Q Richard Lu

Affiliations

Soon will be listed here.

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.

Citing Articles

Hepatocellular Brg1 promotes CCl4-induced liver inflammation, ECM accumulation and fibrosis in mice.

Wang B, Kaufmann B, Mogler C, Zhong S, Yin Y, Cheng Z PLoS One. 2023; 18(11):e0294257.

PMID: 38033027 PMC: 10688683. DOI: 10.1371/journal.pone.0294257.

PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma.

Yao X, Hong J, Nargund A, Ng M, Heng H, Li Z Nat Cell Biol. 2023; 25(5):765-777.

PMID: 37095322 DOI: 10.1038/s41556-023-01122-y.

ACTL6a coordinates axonal caliber recognition and myelination in the peripheral nerve.

Park H, Tsai E, Huang D, Weaver M, Frick L, Alcantara A iScience. 2022; 25(4):104132.

PMID: 35434551 PMC: 9010646. DOI: 10.1016/j.isci.2022.104132.

Conditional Loss of BAF (mSWI/SNF) Scaffolding Subunits Affects Specification and Proliferation of Oligodendrocyte Precursors in Developing Mouse Forebrain.

Abbas E, Hassan M, Sokpor G, Kiszka K, Pham L, Kerimoglu C Front Cell Dev Biol. 2021; 9:619538.

PMID: 34336815 PMC: 8320002. DOI: 10.3389/fcell.2021.619538.

Loss of SWI/SNF Chromatin Remodeling Alters NRF2 Signaling in Non-Small Cell Lung Carcinoma.

Song S, Nguyen V, Schrank T, Mulvaney K, Walter V, Wei D Mol Cancer Res. 2020; 18(12):1777-1788.

PMID: 32855269 PMC: 7718321. DOI: 10.1158/1541-7786.MCR-20-0082.

References

Li B, Carey M, Workman J . The role of chromatin during transcription. Cell. 2007; 128(4):707-19. DOI: 10.1016/j.cell.2007.01.015. View

Edgar J, Garbern J . The myelinated axon is dependent on the myelinating cell for support and maintenance: molecules involved. J Neurosci Res. 2004; 76(5):593-8. DOI: 10.1002/jnr.20063. View

Wu J, Lessard J, Olave I, Qiu Z, Ghosh A, Graef I . Regulation of dendritic development by neuron-specific chromatin remodeling complexes. Neuron. 2007; 56(1):94-108. DOI: 10.1016/j.neuron.2007.08.021. View

Giacinti C, Giordano A . RB and cell cycle progression. Oncogene. 2006; 25(38):5220-7. DOI: 10.1038/sj.onc.1209615. View

Sun S, Ganchi P, Ballard D, Greene W . NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway. Science. 1993; 259(5103):1912-5. DOI: 10.1126/science.8096091. View

Woodhoo A, Alonso M, Droggiti A, Turmaine M, DAntonio M, Parkinson D . Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity. Nat Neurosci. 2009; 12(7):839-47. PMC: 2782951. DOI: 10.1038/nn.2323. View

Schreiner S, Cossais F, Fischer K, Scholz S, Bosl M, Holtmann B . Hypomorphic Sox10 alleles reveal novel protein functions and unravel developmental differences in glial lineages. Development. 2007; 134(18):3271-81. DOI: 10.1242/dev.003350. View

Jacob C, Christen C, Pereira J, Somandin C, Baggiolini A, Lotscher P . HDAC1 and HDAC2 control the transcriptional program of myelination and the survival of Schwann cells. Nat Neurosci. 2011; 14(4):429-36. DOI: 10.1038/nn.2762. View

de la Serna I, Ohkawa Y, Berkes C, Bergstrom D, Dacwag C, Tapscott S . MyoD targets chromatin remodeling complexes to the myogenin locus prior to forming a stable DNA-bound complex. Mol Cell Biol. 2005; 25(10):3997-4009. PMC: 1087700. DOI: 10.1128/MCB.25.10.3997-4009.2005. View

10.

Svaren J, Meijer D . The molecular machinery of myelin gene transcription in Schwann cells. Glia. 2008; 56(14):1541-1551. PMC: 2930200. DOI: 10.1002/glia.20767. View

11.

Wang J, Miller S, Falls D . The N-terminal region of neuregulin isoforms determines the accumulation of cell surface and released neuregulin ectodomain. J Biol Chem. 2000; 276(4):2841-51. DOI: 10.1074/jbc.M005700200. View

12.

Tang L, Nogales E, Ciferri C . Structure and function of SWI/SNF chromatin remodeling complexes and mechanistic implications for transcription. Prog Biophys Mol Biol. 2010; 102(2-3):122-8. PMC: 2924208. DOI: 10.1016/j.pbiomolbio.2010.05.001. View

13.

Marin-Husstege M, Muggironi M, Liu A, Casaccia-Bonnefil P . Histone deacetylase activity is necessary for oligodendrocyte lineage progression. J Neurosci. 2002; 22(23):10333-45. PMC: 6758756. View

14.

Leblanc S, Ward R, Svaren J . Neuropathy-associated Egr2 mutants disrupt cooperative activation of myelin protein zero by Egr2 and Sox10. Mol Cell Biol. 2007; 27(9):3521-9. PMC: 1899967. DOI: 10.1128/MCB.01689-06. View

15.

Ghislain J, Charnay P . Control of myelination in Schwann cells: a Krox20 cis-regulatory element integrates Oct6, Brn2 and Sox10 activities. EMBO Rep. 2005; 7(1):52-8. PMC: 1369227. DOI: 10.1038/sj.embor.7400573. View

16.

de la Serna I, Ohkawa Y, Imbalzano A . Chromatin remodelling in mammalian differentiation: lessons from ATP-dependent remodellers. Nat Rev Genet. 2006; 7(6):461-73. DOI: 10.1038/nrg1882. View

17.

He Y, Kim J, Dupree J, Tewari A, Melendez-Vasquez C, Svaren J . Yy1 as a molecular link between neuregulin and transcriptional modulation of peripheral myelination. Nat Neurosci. 2010; 13(12):1472-80. PMC: 3142946. DOI: 10.1038/nn.2686. View

18.

Finzsch M, Schreiner S, Kichko T, Reeh P, Tamm E, Bosl M . Sox10 is required for Schwann cell identity and progression beyond the immature Schwann cell stage. J Cell Biol. 2010; 189(4):701-12. PMC: 2872908. DOI: 10.1083/jcb.200912142. View

19.

de la Serna I, Carlson K, Imbalzano A . Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation. Nat Genet. 2001; 27(2):187-90. DOI: 10.1038/84826. View

20.

Gebuhr T, Kovalev G, Bultman S, Godfrey V, Su L, Magnuson T . The role of Brg1, a catalytic subunit of mammalian chromatin-remodeling complexes, in T cell development. J Exp Med. 2003; 198(12):1937-49. PMC: 2194157. DOI: 10.1084/jem.20030714. View