Transcriptional regulators of the Golli/myelin basic protein locus integrate additive and stealth activities

Autoři: Hooman Bagheri aff001;  Hana Friedman aff001;  Katherine A. Siminovitch aff002;  Alan C. Peterson aff001
Působiště autorů: Department of Human Genetics, McGill University, Montreal, Quebec, Canada aff001;  Department of Medicine, University of Toronto, Toronto, Ontario, Canada aff002;  Department of Immunology, University of Toronto, Toronto, Ontario, Canada aff003;  Mount Sinai Hospital, Lunenfeld-Tanenbaum and Toronto General Hospital Research Institutes, Toronto, Ontario, Canada aff004;  Gerald Bronfman Department of Oncology, McGill University, Montréal, Québec, Canada aff005;  Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada aff006
Vyšlo v časopise: Transcriptional regulators of the Golli/myelin basic protein locus integrate additive and stealth activities. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008752
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008752


Myelin is composed of plasma membrane spirally wrapped around axons and compacted into dense sheaths by myelin-associated proteins. Myelin is elaborated by neuroepithelial derived oligodendrocytes in the central nervous system (CNS) and by neural crest derived Schwann cells in the peripheral nervous system (PNS). While some myelin proteins accumulate in only one lineage, myelin basic protein (Mbp) is expressed in both. Overlapping the Mbp gene is Golli, a transcriptional unit that is expressed widely both within and beyond the nervous system. A super-enhancer domain within the Golli/Mbp locus contains multiple enhancers shown previously to drive reporter construct expression specifically in oligodendrocytes or Schwann cells. In order to determine the contribution of each enhancer to the Golli/Mbp expression program, and to reveal if functional interactions occur among them, we derived mouse lines in which they were deleted, either singly or in different combinations, and relative mRNA accumulation was measured at key stages of early development and at maturity. Although super-enhancers have been shown previously to facilitate interaction among their component enhancers, the enhancers investigated here demonstrated largely additive relationships. However, enhancers demonstrating autonomous activity strictly in one lineage, when missing, were found to significantly reduce output in the other, thus revealing cryptic “stealth” activity. Further, in the absence of a key oligodendrocyte enhancer, Golli accumulation was markedly and uniformly attenuated in all cell types investigated. Our observations suggest a model in which enhancer-mediated DNA-looping and potential super-enhancer properties underlie Golli/Mbp regulatory organization.

Klíčová slova:

Central nervous system – Chromatin – Messenger RNA – Sciatic nerves – Schwann cells – Spinal cord – Transcriptional control – Zygotes


1. Foran DR, Peterson A. Myelin Acquisition in the Central Nervous System of the Mouse Revealed by an MBP-Lac Z Transgene. The Journal of Neuroscience. 1992;12:4890–7. doi: 10.1523/JNEUROSCI.12-12-04890.1992 1281497

2. Forghani R, Garofalo L, Foran DR, Farhadi HF, Lepage P, Hudson TJ, et al. A Distal Upstream Enhancer from the Myelin Basic Protein Gene Regulated Expression in Myelin-Forming Schwann Cells. The Journal of Neuroscience. 2001;21(11):3780–7. doi: 10.1523/JNEUROSCI.21-11-03780.2001 11356866

3. Bercury KK, Macklin WB. Dynamics and mechanisms of CNS myelination. Dev Cell. 2015;32(4):447–58. Epub 2015/02/25. doi: 10.1016/j.devcel.2015.01.016 25710531; PubMed Central PMCID: PMC6715306.

4. Bergles DE, Richardson WD. Oligodendrocyte Development and Plasticity. Cold Spring Harb Perspect Biol. 2015;8(2). doi: 10.1101/cshperspect.a020453 26492571.

5. Sock E, Wegner M. Transcriptional control of myelination and remyelination. Glia. 2019;67(11):2153–65. Epub 2019/05/01. doi: 10.1002/glia.23636 31038810.

6. Vassall KA, Bamm VV, Harauz G. MyelStones: the executive roles of myelin basic protein in myelin assembly and destabilization in multiple sclerosis. Biochem J. 2015;472(1):17–32. Epub 2015/11/01. doi: 10.1042/BJ20150710 26518750.

7. Bird T, Farrel D.F. and Sumi S.H.,. Genetic development myelin defect in Shiverer mouse. Neurochemistry. 1977;8:153.

8. Rosenbluth J. Central myelin in the mouse mutant Shiverer. The Journal of Comparative Neurology. 1980;194:639–48. doi: 10.1002/cne.901940310 7451686

9. Chernoff G. Shiverer: an autosomal recessive mutant mouse with myelin deficiency. The journal of Heredity. 1981;72:128. doi: 10.1093/oxfordjournals.jhered.a109442 6168677

10. Peterson AC, Bray GM. Hypomyelination in the peripheral nervous system of shiverer mice and in shiverer in equilibrium normal chimaera. The Journal of Comparative Neurology. 1984;227:348–56. doi: 10.1002/cne.902270305 6207210

11. Rosenbluth J. Peripheral myelin in the mouse mutant Shiverer. The Journal of Comparative Neurology. 1980;193:729–39. doi: 10.1002/cne.901930310 7440788

12. Gould RM, Byrd AL, Barbarese E. The number of Schmidt-Lanterman incisures is more than doubled in shiverer PNS myelin sheaths. Journal of Neurocytology. 1995;24:85–98. doi: 10.1007/BF01181552 7745445

13. Smith-Slatas C, Barbarese E. Myelin basic protein gene dosage effects in the PNS. Molecular and cellular neurosciences. 2000;15(4):343–54. doi: 10.1006/mcne.1999.0829 10845771.

14. Popko B, Puckett C, Lai E, Shine H, Readhead C, Takahashi N, et al. Myelin deficient mice: expression of myelin basic protein and generation of mice with varying levels of myelin. Cell. 1987;48:713–21. doi: 10.1016/0092-8674(87)90249-2 2434243

15. Shine HD, Readhead C, Popko B, Hood L, Sidman RL. Morphometric Analysis of Normal, Mutant, and Transgenic CNS: Correlation of Myelin Basic Protein Expression to Myelinogenesis. Journal of Neurochemistry. 1992;58(1):342–9. doi: 10.1111/j.1471-4159.1992.tb09316.x 1370079

16. Campagnoni A, Pribyl T, Campagnoni C, Kampf K, Amur-Umarjee S, Landry C, et al. Structure and developmental regulation of Golli-mbp, a 105-kilobase gene that encompasses the myelin basic protein gene and is expressed in cells in the oligodendrocyte lineage in the brain. Biological chemistry. 1993;268:4930–8.

17. Feng JM, Fernandes AO, Campagnoni CW, Hu YH, Campagnoni AT. The golli-myelin basic protein negatively regulates signal transduction in T lymphocytes. J Neuroimmunol. 2004;152(1–2):57–66. doi: 10.1016/j.jneuroim.2004.03.021 15223237.

18. Feng JM, Givogri IM, Bongarzone ER, Campagnoni C, Jacobs E, Handley VW, et al. Thymocytes Express the golli Products of the Myelin Basic Protein Gene and Levels of Expression Are Stage Dependent. The Journal of Immunology. 2000;165(10):5443–50. doi: 10.4049/jimmunol.165.10.5443 11067896

19. Feng JM, Hu YK, Xie LH, Colwell CS, Shao XM, Sun XP, et al. Golli protein negatively regulates store depletion-induced calcium influx in T cells. Immunity. 2006;24(6):717–27. doi: 10.1016/j.immuni.2006.04.007 16782028.

20. Paez PM, Cheli VT, Ghiani CA, Spreuer V, Handley VW, Campagnoni AT. Golli myelin basic proteins stimulate oligodendrocyte progenitor cell proliferation and differentiation in remyelinating adult mouse brain. Glia. 2012;60(7):1078–93. Epub 2012/03/27. doi: 10.1002/glia.22336 22447683.

21. Paez PM, Fulton DJ, Spreuer V, Handley V, Campagnoni CW, Campagnoni AT. Regulation of store-operated and voltage-operated Ca2+ channels in the proliferation and death of oligodendrocyte precursor cells by golli proteins. ASN Neuro. 2009;1(1). doi: 10.1042/AN20090003 19570024; PubMed Central PMCID: PMC2695580.

22. Vt C, Da SG, V S, V H, At C, Pm P. Golli Myelin Basic Proteins Modulate Voltage-Operated Ca(++) Influx and Development in Cortical and Hippocampal Neurons. Mol Neurobiol. 2016;53(8):5749–71. doi: 10.1007/s12035-015-9499-1 26497031; PubMed Central PMCID: PMC4882270.

23. Berndt JA, Kim JG, Tosic M, Kim C, Hudson LD. The transcriptional regulator Yin Yang 1 activates the myelin PLP gene. Journal of Neurochemistry. 2001;77(3):935–42. doi: 10.1046/j.1471-4159.2001.00307.x 11331422

24. Wang SZ, Dulin J, Wu H, Hurlock E, Lee SE, Jansson K, et al. An oligodendrocyte-specific zinc-finger transcription regulator cooperates with Olig2 to promote oligodendrocyte differentiation. Development. 2006;133(17):3389–98. doi: 10.1242/dev.02522 16908628.

25. Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2008;28(1):264–78. doi: 10.1523/JNEUROSCI.4178-07.2008 18171944.

26. Svaren J, Meijer D. The molecular machinery of myelin gene transcription in Schwann cells. Glia. 2008;56(14):1541–51. doi: 10.1002/glia.20767 18803322; PubMed Central PMCID: PMC2930200.

27. Emery B, Agalliu D, Cahoy JD, Watkins TA, Dugas JC, Mulinyawe SB, et al. Myelin gene regulatory factor is a critical transcriptional regulator required for CNS myelination. Cell. 2009;138(1):172–85. doi: 10.1016/j.cell.2009.04.031 19596243; PubMed Central PMCID: PMC2757090.

28. Ahrendsen JT, Macklin W. Signaling mechanisms regulating myelination in the central nervous system. Neuroscience Bulletin. 2013;29(2):199–215. doi: 10.1007/s12264-013-1322-2 23558589

29. Vogl MR, Reiprich S, Kuspert M, Kosian T, Schrewe H, Nave KA, et al. Sox10 cooperates with the mediator subunit 12 during terminal differentiation of myelinating glia. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2013;33(15):6679–90. doi: 10.1523/JNEUROSCI.5178-12.2013 23575864.

30. Hung HA, Sun G, Keles S, Svaren J. Dynamic regulation of Schwann cell enhancers after peripheral nerve injury. The Journal of biological chemistry. 2015;290(11):6937–50. doi: 10.1074/jbc.M114.622878 25614629; PubMed Central PMCID: PMC4358118.

31. Stolt CC, Wegner M. Schwann cells and their transcriptional network: Evolution of key regulators of peripheral myelination. Brain Res. 2015. doi: 10.1016/j.brainres.2015.09.025 26423937.

32. Weider M, Wegner M. SoxE factors: Transcriptional regulators of neural differentiation and nervous system development. Seminars in cell & developmental biology. 2017;63:35–42. Epub 2016/08/25. doi: 10.1016/j.semcdb.2016.08.013 27552919.

33. Jang SW, Srinivasan R, Jones EA, Sun G, Keles S, Krueger C, et al. Locus-wide identification of Egr2/Krox20 regulatory targets in myelin genes. J Neurochem. 2010;115(6):1409–20. doi: 10.1111/j.1471-4159.2010.07045.x 21044070; PubMed Central PMCID: PMC3260055.

34. Srinivasan R, Sun G, Keles S, Jones EA, Jang SW, Krueger C, et al. Genome-wide analysis of EGR2/SOX10 binding in myelinating peripheral nerve. Nucleic acids research. 2012;40(14):6449–60. doi: 10.1093/nar/gks313 22492709; PubMed Central PMCID: PMC3413122.

35. Aaker JD, Elbaz B, Wu Y, Looney TJ, Zhang L, Lahn BT, et al. Transcriptional Fingerprint of Hypomyelination in Zfp191null and Shiverer (Mbpshi) Mice. ASN Neuro. 2016;8(5). Epub 2016/09/30. doi: 10.1177/1759091416670749 27683878; PubMed Central PMCID: PMC5046175.

36. Elbaz B, Aaker JD, Isaac S, Kolarzyk A, Brugarolas P, Eden A, et al. Phosphorylation State of ZFP24 Controls Oligodendrocyte Differentiation. Cell reports. 2018;23(8):2254–63. Epub 2018/05/24. doi: 10.1016/j.celrep.2018.04.089 29791837; PubMed Central PMCID: PMC6002757.

37. Howng SY, Avila RL, Emery B, Traka M, Lin W, Watkins T, et al. ZFP191 is required by oligodendrocytes for CNS myelination. Genes Dev. 2010;24(3):301–11. Epub 2010/01/19. doi: 10.1101/gad.1864510 20080941; PubMed Central PMCID: PMC2811831.

38. Cantone M, Kuspert M, Reiprich S, Lai X, Eberhardt M, Gottle P, et al. A gene regulatory architecture that controls region-independent dynamics of oligodendrocyte differentiation. Glia. 2019;67(5):825–43. Epub 2019/02/08. doi: 10.1002/glia.23569 30730593.

39. Chen Y, Wang H, Yoon SO, Xu X, Hottiger MO, Svaren J, et al. HDAC-mediated deacetylation of NF-kappaB is critical for Schwann cell myelination. Nature neuroscience. 2011;14(4):437–41. doi: 10.1038/nn.2780 21423191; PubMed Central PMCID: PMC3074381.

40. Weider M, Reiprich S, Wegner M. Sox appeal—Sox10 attracts epigenetic and transcriptional regulators in myelinating glia. Biological chemistry. 2013;394(12):1583–93. doi: 10.1515/hsz-2013-0146 23729567.

41. Emery B, Lu QR. Transcriptional and Epigenetic Regulation of Oligodendrocyte Development and Myelination in the Central Nervous System. Cold Spring Harb Perspect Biol. 2015;7(9):a020461. Epub 2015/07/03. doi: 10.1101/cshperspect.a020461 26134004; PubMed Central PMCID: PMC4563712.

42. Scaglione A, Patzig J, Liang J, Frawley R, Bok J, Mela A, et al. PRMT5-mediated regulation of developmental myelination. Nat Commun. 2018;9(1):2840. Epub 2018/07/22. doi: 10.1038/s41467-018-04863-9 30026560; PubMed Central PMCID: PMC6053423.

43. Tiane A, Schepers M, Rombaut B, Hupperts R, Prickaerts J, Hellings N, et al. From OPC to Oligodendrocyte: An Epigenetic Journey. Cells. 2019;8(10). Epub 2019/10/17. doi: 10.3390/cells8101236 31614602.

44. TheEncodeProjectConsortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57–74. Epub 2012/09/08. doi: 10.1038/nature11247 22955616; PubMed Central PMCID: PMC3439153.

45. Sabari BR, Dall'Agnese A, Boija A, Klein IA, Coffey EL, Shrinivas K, et al. Coactivator condensation at super-enhancers links phase separation and gene control. Science. 2018;361(6400). Epub 2018/06/23. doi: 10.1126/science.aar3958 29930091; PubMed Central PMCID: PMC6092193.

46. Hnisz D, Shrinivas K, Young RA, Chakraborty AK, Sharp PA. A Phase Separation Model for Transcriptional Control. Cell. 2017;169(1):13–23. doi: 10.1016/j.cell.2017.02.007 28340338; PubMed Central PMCID: PMC5432200.

47. Gurumurthy A, Shen Y, Gunn EM, Bungert J. Phase Separation and Transcription Regulation: Are Super-Enhancers and Locus Control Regions Primary Sites of Transcription Complex Assembly? Bioessays. 2019;41(1):e1800164. Epub 2018/12/01. doi: 10.1002/bies.201800164 30500078; PubMed Central PMCID: PMC6484441.

48. Denarier E, Forghani R, Farhadi HF, Dib S, Dionne N, Friedman HC, et al. Functional organization of a Schwann cell enhancer. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2005;25(48):11210–7. doi: 10.1523/JNEUROSCI.2596-05.2005 16319321.

49. Dib S, Denarier E, Dionne N, Beaudoin M, Friedman HH, Peterson AC. Regulatory modules function in a non-autonomous manner to control transcription of the mbp gene. Nucleic acids research. 2011;39(7):2548–58. doi: 10.1093/nar/gkq1160 21131280; PubMed Central PMCID: PMC3074125.

50. Dionne N, Dib S, Finsen B, Denarier E, Kuhlmann T, Drouin R, et al. Functional organization of an Mbp enhancer exposes striking transcriptional regulatory diversity within myelinating glia. Glia. 2016;64(1):175–94. doi: 10.1002/glia.22923 26507463.

51. Bujalka H, Koenning M, Jackson S, Perreau VM, Pope B, Hay CM, et al. MYRF is a membrane-associated transcription factor that autoproteolytically cleaves to directly activate myelin genes. PLoS Biol. 2013;11(8):e1001625. doi: 10.1371/journal.pbio.1001625 23966833; PubMed Central PMCID: PMC3742440.

52. Lopez-Anido C, Sun G, Koenning M, Srinivasan R, Hung HA, Emery B, et al. Differential Sox10 genomic occupancy in myelinating glia. Glia. 2015. doi: 10.1002/glia.22855 25974668; PubMed Central PMCID: PMC4644515.

53. Farhadi HF, Lepage P, Forghani R, Friedman HCH, Orfali W, Jasmin L, et al. A Combinatorial Network of Evolutionarily Conserved Myelin Basic Protein Regulatory Sequence Confers Distinct Gial-Specific Phenotypes. Neurosciene. 2003;23(32):10214–23.

54. Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, et al. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell. 2013;153(2):307–19. Epub 2013/04/16. doi: 10.1016/j.cell.2013.03.035 23582322; PubMed Central PMCID: PMC3653129.

55. Khan A, Zhang X. dbSUPER: a database of super-enhancers in mouse and human genome. Nucleic acids research. 2016;44(D1):D164–D71. doi: 10.1093/nar/gkv1002 26438538

56. Nolis IK, McKay DJ, Mantouvalou E, Lomvardas S, Merika M, Thanos D. Transcription factors mediate long-range enhancer–promoter interactions. Proceedings of the National Academy of Sciences. 2009;106(48):20222–7. doi: 10.1073/pnas.0902454106 19923429

57. Bu J, Banki A, Wu Q, Nishiyama A. Increased NG2(+) glial cell proliferation and oligodendrocyte generation in the hypomyelinating mutant shiverer. Glia. 2004;48(1):51–63. doi: 10.1002/glia.20055 15326615.

58. Fulton DL, Denarier E, Friedman HC, Wasserman WW, Peterson AC. Towards resolving the transcription factor network controlling myelin gene expression. Nucleic acids research. 2011;39(18):7974–91. doi: 10.1093/nar/gkr326 21729871; PubMed Central PMCID: PMC3185407.

59. Yu Y, Chen Y, Kim B, Wang H, Zhao C, He X, et al. Olig2 targets chromatin remodelers to enhancers to initiate oligodendrocyte differentiation. Cell. 2013;152(1–2):248–61. doi: 10.1016/j.cell.2012.12.006 23332759; PubMed Central PMCID: PMC3553550.

60. Readhead C, Popko B, Takahashi N, Shine H, Saavedra R, Sidman R, et al. Expression of a myelin basic protein gene in transgenic shiverer mice: correction of the dysmyelinating phenotype. Cell Press. 1987;48:713–21.

61. Mathisen PM, Pease S, Garvey J, Hood L, Readhead C. Identification of an embryonic isoform of myelin basic protein that is expressed widely in the mouse embryo. Proceedings of the National Academy of Sciences. 1993;90(21):10125–9. doi: 10.1073/pnas.90.21.10125 7694281

62. Filipovic R, Rakic S, Zecevic N. Expression of Golli proteins in adult human brain and multiple sclerosis lesions. Journal of Neuroimmunology. 2002;127(1):1–12. doi:

63. Landry C, Ellison J, Pribyl T, Campagnoni C, Kampf K, Campagnoni A. Myelin basic protein gene expression in neurons: developmental and regional changes in protein targeting within neuronal nuclei, cell bodies, and processes. The Journal of Neuroscience. 1996;16(8):2452–62. doi: 10.1523/JNEUROSCI.16-08-02452.1996 8786422

64. Landry CF, Ellison J, Skinner E, Campagnoni AT. Golli-MBP proteins mark the earliest stages of fiber extension and terminal arboration in the mouse peripheral nervous system. Journal of Neuroscience Research. 1997;50(2):265–71. doi: 10.1002/(SICI)1097-4547(19971015)50:2<265::AID-JNR15>3.0.CO;2-7 9373036

65. Landry CF, Pribyl TM, Ellison JA, Givogri MI, Kampf K, Campagnoni CW, et al. Embryonic Expression of the Myelin Basic Protein Gene: Identification of a Promoter Region That Targets Transgene Expression to Pioneer Neurons. The Journal of Neuroscience. 1998;18(18):7315–27. doi: 10.1523/JNEUROSCI.18-18-07315.1998 9736652

66. Feng JM. Minireview: expression and function of golli protein in immune system. Neurochem Res. 2007;32(2):273–8. doi: 10.1007/s11064-006-9164-1 17024569.

67. Lorente Pons A, Higginbottom A, Cooper-Knock J, Alrafiah A, Alofi E, Kirby J, et al. Oligodendrocyte pathology exceeds axonal pathology in white matter in human amyotrophic lateral sclerosis. The Journal of Pathology. n/a(n/a). doi: 10.1002/path.5455 32391572

68. Uschkureit T, Spörkel O, Stracke J, Büssow H, Stoffel W. Early Onset of Axonal Degeneration in Double (plp−/−mag−/−) and Hypomyelinosis in Triple (plp−/−mbp−/−mag−/−) Mutant Mice. The Journal of Neuroscience. 2000;20(14):5225–33. doi: 10.1523/JNEUROSCI.20-14-05225.2000 10884306

69. Wiktorowicz M, Roach A. Regulation of Myelin Basic Protein Gene Transcription in Normal and shiverer Mutant Mice. Developmental neuroscience. 1991;13(3):143–50. doi: 10.1159/000112152 1721568

70. Dowen JM, Fan ZP, Hnisz D, Ren G, Abraham BJ, Zhang LN, et al. Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes. Cell. 2014;159(2):374–87. Epub 2014/10/11. doi: 10.1016/j.cell.2014.09.030 25303531; PubMed Central PMCID: PMC4197132.

71. Hnisz D, Abraham BJ, Lee TI, Lau A, Saint-Andre V, Sigova AA, et al. Super-enhancers in the control of cell identity and disease. Cell. 2013;155(4):934–47. doi: 10.1016/j.cell.2013.09.053 24119843; PubMed Central PMCID: PMC3841062.

72. Pott S, Lieb JD. What are super-enhancers? Nat Genet. 2015;47(1):8–12. Epub 2014/12/31. doi: 10.1038/ng.3167 25547603.

73. Quevedo M, Meert L, Dekker MR, Dekkers DHW, Brandsma JH, van den Berg DLC, et al. Mediator complex interaction partners organize the transcriptional network that defines neural stem cells. Nat Commun. 2019;10(1):2669. Epub 2019/06/19. doi: 10.1038/s41467-019-10502-8 31209209; PubMed Central PMCID: PMC6573065.

74. Shen Y, Yue F, McCleary DF, Ye Z, Edsall L, Kuan S, et al. A map of the cis-regulatory sequences in the mouse genome. Nature. 2012;488(7409):116–20. doi: 10.1038/nature11243 22763441; PubMed Central PMCID: PMC4041622.

75. Hay D, Hughes JR, Babbs C, Davies JOJ, Graham BJ, Hanssen L, et al. Genetic dissection of the alpha-globin super-enhancer in vivo. Nat Genet. 2016;48(8):895–903. Epub 2016/07/05. doi: 10.1038/ng.3605 27376235; PubMed Central PMCID: PMC5058437.

76. Huang J, Li K, Cai W, Liu X, Zhang Y, Orkin SH, et al. Dissecting super-enhancer hierarchy based on chromatin interactions. Nat Commun. 2018;9(1):943. Epub 2018/03/07. doi: 10.1038/s41467-018-03279-9 29507293; PubMed Central PMCID: PMC5838163.

77. Bender MA, Roach JN, Halow J, Close J, Alami R, Bouhassira EE, et al. Targeted deletion of 5′HS1 and 5′HS4 of the β-globin locus control region reveals additive activity of the DNaseI hypersensitive sites. Blood. 2001;98(7):2022–7. doi: 10.1182/blood.v98.7.2022 11567985

78. Fang X, Sun J, Xiang P, Yu M, Navas PA, Peterson KR, et al. Synergistic and Additive Properties of the Beta-Globin Locus Control Region (LCR) Revealed by 5′HS3 Deletion Mutations: Implication for LCR Chromatin Architecture. Molecular and Cellular Biology. 2005;25(16):7033–41. doi: 10.1128/MCB.25.16.7033-7041.2005 16055715

79. Dukler N, Gulko B, Huang YF, Siepel A. Is a super-enhancer greater than the sum of its parts? Nat Genet. 2016;49(1):2–3. Epub 2016/12/29. doi: 10.1038/ng.3759 28029159; PubMed Central PMCID: PMC5379849.

80. Allahyar A, Vermeulen C, Bouwman BAM, Krijger PHL, Verstegen M, Geeven G, et al. Enhancer hubs and loop collisions identified from single-allele topologies. Nat Genet. 2018;50(8):1151–60. Epub 2018/07/11. doi: 10.1038/s41588-018-0161-5 29988121.

81. Koenning M, Jackson S, Hay CM, Faux C, Kilpatrick TJ, Willingham M, et al. Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2012;32(36):12528–42. doi: 10.1523/JNEUROSCI.1069-12.2012 22956843; PubMed Central PMCID: PMC3752083.

82. Hornig J, Frob F, Vogl MR, Hermans-Borgmeyer I, Tamm ER, Wegner M. The transcription factors Sox10 and Myrf define an essential regulatory network module in differentiating oligodendrocytes. PLoS genetics. 2013;9(10):e1003907. doi: 10.1371/journal.pgen.1003907 24204311; PubMed Central PMCID: PMC3814293.

83. Dai J, Bercury KK, Ahrendsen JT, Macklin WB. Olig1 function is required for oligodendrocyte differentiation in the mouse brain. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2015;35(10):4386–402. Epub 2015/03/13. doi: 10.1523/JNEUROSCI.4962-14.2015 25762682; PubMed Central PMCID: PMC4461695.

84. Arnett HA, Fancy SPJ, Alberta JA, Zhao C, Plant SR, Kaing S, et al. bHLH Transcription Factor Olig1 Is Required to Repair Demyelinated Lesions in the CNS. Science. 2004;306(5704):2111–5. doi: 10.1126/science.1103709 15604411

85. Jacob C, Lotscher P, Engler S, Baggiolini A, Varum Tavares S, Brugger V, et al. HDAC1 and HDAC2 control the specification of neural crest cells into peripheral glia. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2014;34(17):6112–22. doi: 10.1523/JNEUROSCI.5212-13.2014 24760871; PubMed Central PMCID: PMC3996228.

86. Ye F, Chen Y, Hoang T, Montgomery RL, Zhao XH, Bu H, et al. HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction. Nature neuroscience. 2009;12(7):829–38. doi: 10.1038/nn.2333 19503085; PubMed Central PMCID: PMC2701973.

87. Quintes S, Brinkmann BG, Ebert M, Frob F, Kungl T, Arlt FA, et al. Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair. Nature neuroscience. 2016;19(8):1050–9. Epub 2016/06/14. doi: 10.1038/nn.4321 27294512; PubMed Central PMCID: PMC4964942.

88. He Y, Dupree J, Wang J, Sandoval J, Li J, Liu H, et al. The transcription factor Yin Yang 1 is essential for oligodendrocyte progenitor differentiation. Neuron. 2007;55(2):217–30. Epub 2007/07/21. doi: 10.1016/j.neuron.2007.06.029 17640524; PubMed Central PMCID: PMC2034312.

89. He Y, Kim JY, Dupree J, Tewari A, Melendez-Vasquez C, Svaren J, et al. Yy1 as a molecular link between neuregulin and transcriptional modulation of peripheral myelination. Nature neuroscience. 2010;13(12):1472–80. Epub 2010/11/09. doi: 10.1038/nn.2686 21057508; PubMed Central PMCID: PMC3142946.

90. Liu J, Magri L, Zhang F, Marsh NO, Albrecht S, Huynh JL, et al. Chromatin landscape defined by repressive histone methylation during oligodendrocyte differentiation. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2015;35(1):352–65. Epub 2015/01/09. doi: 10.1523/JNEUROSCI.2606-14.2015 25568127; PubMed Central PMCID: PMC4287153.

91. Zabidi MA, Arnold CD, Schernhuber K, Pagani M, Rath M, Frank O, et al. Enhancer-core-promoter specificity separates developmental and housekeeping gene regulation. Nature. 2015;518(7540):556–9. doi: 10.1038/nature13994 25517091.

92. Zabidi MA, Stark A. Regulatory Enhancer-Core-Promoter Communication via Transcription Factors and Cofactors. Trends Genet. 2016;32(12):801–14. doi: 10.1016/j.tig.2016.10.003 27816209.

93. Inukai S, Kock KH, Bulyk ML. Transcription factor-DNA binding: beyond binding site motifs. Curr Opin Genet Dev. 2017;43:110–9. doi: 10.1016/j.gde.2017.02.007 28359978; PubMed Central PMCID: PMC5447501.

94. Ma KH, Svaren J. Epigenetic Control of Schwann Cells. Neuroscientist. 2018;24(6):627–38. Epub 2018/01/09. doi: 10.1177/1073858417751112 29307265.

95. Deng W, Lee J, Wang H, Miller J, Reik A, Gregory PD, et al. Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor. Cell. 2012;149(6):1233–44. doi: 10.1016/j.cell.2012.03.051 22682246; PubMed Central PMCID: PMC3372860.

96. Levine M, Cattoglio C, Tjian R. Looping back to leap forward: transcription enters a new era. Cell. 2014;157(1):13–25. doi: 10.1016/j.cell.2014.02.009 24679523; PubMed Central PMCID: PMC4059561.

97. Vietri Rudan M, Hadjur S. Genetic Tailors: CTCF and Cohesin Shape the Genome During Evolution. Trends Genet. 2015;31(11):651–60. doi: 10.1016/j.tig.2015.09.004 26439501.

98. Weintraub AS, Li CH, Zamudio AV, Sigova AA, Hannett NM, Day DS, et al. YY1 Is a Structural Regulator of Enhancer-Promoter Loops. Cell. 2017;171(7):1573–88 e28. Epub 2017/12/12. doi: 10.1016/j.cell.2017.11.008 29224777; PubMed Central PMCID: PMC5785279.

99. Su W, Jackson S, Tjian R, Echols H. DNA looping between sites for transcriptional activation: self-association of DNA-bound Sp1. Genes Dev. 1991;5(5):820–6. Epub 1991/05/01. doi: 10.1101/gad.5.5.820 1851121.

100. Khan A, Fornes O, Stigliani A, Gheorghe M, Castro-Mondragon JA, van der Lee R, et al. JASPAR 2018: update of the open-access database of transcription factor binding profiles and its web framework. Nucleic acids research. 2018;46(D1):D260–D6. Epub 2017/11/16. doi: 10.1093/nar/gkx1126 29140473; PubMed Central PMCID: PMC5753243.

101. Arthur-Farraj P, Moyon S. DNA methylation in Schwann cells and in oligodendrocytes. Glia. 2020. Epub 2020/01/21. doi: 10.1002/glia.23784 31958184.

102. Kim J, Kim J. YY1's longer DNA-binding motifs. Genomics. 2009;93(2):152–8. Epub 2008/10/28. doi: 10.1016/j.ygeno.2008.09.013 18950698; PubMed Central PMCID: PMC2668202.

103. Guo L, Eviatar-Ribak T, Miskimins R. Sp1 phosphorylation is involved in myelin basic protein gene transcription. J Neurosci Res. 2010;88(15):3233–42. Epub 2010/10/01. doi: 10.1002/jnr.22486 20882567.

104. Tretiakova A, Steplewski A, Johnson EM, Khalili K, Amini S. Regulation of myelin basic protein gene transcription by Sp1 and Purα: Evidence for association of Sp1 and Purα in brain. Journal of Cellular Physiology. 1999;181(1):160–8. doi: 10.1002/(SICI)1097-4652(199910)181:1<160::AID-JCP17>3.0.CO;2-H 10457364

105. Pan MR, Hung WC. Nonsteroidal anti-inflammatory drugs inhibit matrix metalloproteinase-2 via suppression of the ERK/Sp1-mediated transcription. The Journal of biological chemistry. 2002;277(36):32775–80. Epub 2002/06/28. doi: 10.1074/jbc.M202334200 12087091.

106. Bechler ME, Byrne L, Ffrench-Constant C. CNS Myelin Sheath Lengths Are an Intrinsic Property of Oligodendrocytes. Curr Biol. 2015;25(18):2411–6. Epub 2015/09/01. doi: 10.1016/j.cub.2015.07.056 26320951; PubMed Central PMCID: PMC4580335.

107. Snaidero N, Simons M. Myelination at a glance. J Cell Sci. 2014;127(Pt 14):2999–3004. Epub 2014/07/16. doi: 10.1242/jcs.151043 25024457.

108. Fields RD. A new mechanism of nervous system plasticity: activity-dependent myelination. Nat Rev Neurosci. 2015;16(12):756–67. doi: 10.1038/nrn4023 26585800.

109. Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 2013;31(9):827–32. Epub 2013/07/23. doi: 10.1038/nbt.2647 23873081.

110. Hwang WY, Fu Y, Reyon D, Maeder ML, Tsai SQ, Sander JD, et al. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nat Biotechnol. 2013;31(3):227–9. doi: 10.1038/nbt.2501 23360964; PubMed Central PMCID: PMC3686313.

111. Bassett AR, Tibbit C, Ponting CP, Liu JL. Highly efficient targeted mutagenesis of Drosophila with the CRISPR/Cas9 system. Cell reports. 2013;4(1):220–8. doi: 10.1016/j.celrep.2013.06.020 23827738; PubMed Central PMCID: PMC3714591.

112. Tuason MC, Rastikerdar A, Kuhlmann T, Goujet-Zalc C, Zalc B, Dib S, et al. Separate proteolipid protein/DM20 enhancers serve different lineages and stages of development. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2008;28(27):6895–903. doi: 10.1523/JNEUROSCI.4579-07.2008 18596164.

113. Wang W, Kutny PM, Byers SL, Longstaff CJ, DaCosta MJ, Pang C, et al. Delivery of Cas9 Protein into Mouse Zygotes through a Series of Electroporation Dramatically Increases the Efficiency of Model Creation. J Genet Genomics. 2016;43(5):319–27. doi: 10.1016/j.jgg.2016.02.004 27210041; PubMed Central PMCID: PMC4892940.

114. Wang W, Zhang Y, Wang H. Generating Mouse Models Using Zygote Electroporation of Nucleases (ZEN) Technology with High Efficiency and Throughput. Methods Mol Biol. 2017;1605:219–30. doi: 10.1007/978-1-4939-6988-3_15 28456968.

Článek vyšel v časopise

PLOS Genetics

2020 Číslo 8

Nejčtenější v tomto čísle

Zvyšte si kvalifikaci online z pohodlí domova

Možnosti biologické léčby u CRSwNP
nový kurz
Autoři: MUDr. Zuzana Balatková, Ph.D.

Magnetická rezonance a diagnostika axiálních spondyloartritid - Virtuální trénink
Autoři: MUDr. Leona Procházková, Ph.D., MUDr. Monika Gregová, Ph.D., MUDr. Vladimír Červeňák, MUDr. Eva Korčáková, Ph.D.

Eozinofilní granulomatóza s polyangiitidou

Betablokátory a Ca antagonisté z jiného úhlu
Autoři: prof. MUDr. Michal Vrablík, Ph.D., MUDr. Petr Janský

Urtikarie – přehled o onemocnění a léčbě a významu antihistaminik

Všechny kurzy
Kurzy Podcasty Doporučená témata Časopisy
Zapomenuté heslo

Nemáte účet?  Registrujte se

Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se