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PLoS genetics
06, 2022;18 (6): e1010235.

Enhanced transcriptional heterogeneity mediated by NF-κB super-enhancers.

Johannes N Wibisana, Takehiko Inaba, Hisaaki Shinohara, Noriko Yumoto, Tetsutaro Hayashi, Mana Umeda, Masashi Ebisawa, Itoshi Nikaido, Yasushi Sako, Mariko Okada
Author Information
  1. Johannes N Wibisana: Laboratory for Cell Systems, Institute for Protein Research, Osaka University, Yamadaoka, Suita, Osaka, Japan. ORCID
  2. Takehiko Inaba: Cellular Informatics Laboratory, RIKEN, Wako, Saitama, Japan.
  3. Hisaaki Shinohara: RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan. ORCID
  4. Noriko Yumoto: RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
  5. Tetsutaro Hayashi: Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan. ORCID
  6. Mana Umeda: Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan. ORCID
  7. Masashi Ebisawa: Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan. ORCID
  8. Itoshi Nikaido: Laboratory for Bioinformatics Research, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan. ORCID
  9. Yasushi Sako: Cellular Informatics Laboratory, RIKEN, Wako, Saitama, Japan. ORCID
  10. Mariko Okada: Laboratory for Cell Systems, Institute for Protein Research, Osaka University, Yamadaoka, Suita, Osaka, Japan.
PMID: 35648786 DOI: 10.1371/journal.pgen.1010235

Abstract

The transcription factor NF-κB, which plays an important role in cell fate determination, is involved in the activation of super-enhancers (SEs). However, the biological functions of the NF-κB SEs in gene control are not fully elucidated. We investigated the characteristics of NF-κB-mediated SE activity using fluorescence imaging of RelA, single-cell transcriptome and chromatin accessibility analyses in anti-IgM-stimulated B cells. The formation of cell stimulation-induced nuclear RelA foci was abolished in the presence of hexanediol, suggesting an underlying process of liquid-liquid phase separation. The gained SEs induced a switch-like expression and enhanced cell-to-cell variability in transcriptional response. These properties were correlated with the number of gained cis-regulatory interactions, while switch-like gene induction was associated with the number of NF-κB binding sites in SE. Our study suggests that NF-κB SEs have an important role in the transcriptional regulation of B cells possibly through liquid condensate formation consisting of macromolecular interactions.

References

  1. Bioinformatics. 2014 Apr 1;30(7):923-30 [PMID: 24227677]
  2. Trends Immunol. 2004 Jun;25(6):280-8 [PMID: 15145317]
  3. Molecules. 2018 Aug 06;23(8): [PMID: 30082609]
  4. Cell. 2013 Nov 7;155(4):934-47 [PMID: 24119843]
  5. Sci Rep. 2016 Jun 09;6:27706 [PMID: 27277891]
  6. Cells. 2019 Dec 19;9(1): [PMID: 31861624]
  7. Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11644-9 [PMID: 20534546]
  8. Science. 2016 Jan 1;351(6268):84-8 [PMID: 26628643]
  9. Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):E2888-E2897 [PMID: 29514960]
  10. Methods Mol Biol. 2016;1418:335-51 [PMID: 27008022]
  11. Oncogene. 2014 May 1;33(18):2395-404 [PMID: 23686307]
  12. Mol Cell. 2018 Sep 6;71(5):858-871.e8 [PMID: 30078726]
  13. Bioinformatics. 2020 Feb 15;36(4):1174-1181 [PMID: 31584606]
  14. Genes Dev. 2012 Feb 1;26(3):203-34 [PMID: 22302935]
  15. Immunity. 2006 Nov;25(5):701-15 [PMID: 17098202]
  16. Cell Syst. 2018 Oct 24;7(4):384-397.e6 [PMID: 30243562]
  17. Genes Dev. 2015 Jan 15;29(2):197-211 [PMID: 25593309]
  18. Nat Commun. 2018 Feb 12;9(1):619 [PMID: 29434199]
  19. Bioinformatics. 2011 Apr 1;27(7):1017-8 [PMID: 21330290]
  20. Immunol Rev. 2012 Mar;246(1):221-38 [PMID: 22435558]
  21. Cell Rep. 2020 Jun 2;31(9):107724 [PMID: 32492432]
  22. Science. 2018 Jul 27;361(6400): [PMID: 29930091]
  23. Cell Syst. 2017 Nov 22;5(5):471-484.e4 [PMID: 29102610]
  24. Cell Rep. 2018 Jan 16;22(3):585-599 [PMID: 29346759]
  25. OMICS. 2012 May;16(5):284-7 [PMID: 22455463]
  26. Nat Genet. 2015 Jan;47(1):8-12 [PMID: 25547603]
  27. Sci Adv. 2021 Jan 1;7(1): [PMID: 33523844]
  28. Nat Commun. 2018 Mar 5;9(1):943 [PMID: 29507293]
  29. Nat Biotechnol. 2020 Mar;38(3):276-278 [PMID: 32055031]
  30. Bioessays. 2016 Feb;38(2):172-80 [PMID: 26625861]
  31. Cell. 2018 Dec 13;175(7):1842-1855.e16 [PMID: 30449618]
  32. Curr Opin Immunol. 2002 Jun;14(3):341-7 [PMID: 11973132]
  33. Science. 2014 May 16;344(6185):760-4 [PMID: 24833394]
  34. Genome Biol. 2019 Feb 21;20(1):42 [PMID: 30791920]
  35. Science. 2012 Apr 13;336(6078):183-7 [PMID: 22499939]
  36. Trends Genet. 2020 Apr;36(4):288-297 [PMID: 32035656]
  37. J Biol Chem. 1992 Sep 5;267(25):17971-6 [PMID: 1381359]
  38. Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):2144-2149 [PMID: 29444854]
  39. Cell. 2013 Apr 11;153(2):320-34 [PMID: 23582323]
  40. Mol Cell. 2019 Aug 8;75(3):549-561.e7 [PMID: 31398323]
  41. Proteins. 2001 Jan 1;42(1):38-48 [PMID: 11093259]
  42. Mol Cell. 2019 Dec 5;76(5):753-766.e6 [PMID: 31563432]
  43. Cell. 2013 Apr 11;153(2):307-19 [PMID: 23582322]
  44. Science. 2018 Mar 2;359(6379):1050-1055 [PMID: 29371426]
  45. Nat Biotechnol. 2018 Jun;36(5):411-420 [PMID: 29608179]
  46. Bioinformatics. 2013 Jan 1;29(1):15-21 [PMID: 23104886]
  47. Methods Mol Biol. 2016;1357:111-31 [PMID: 26025620]
  48. Nat Methods. 2013 Apr;10(4):277-8 [PMID: 23538861]
  49. Elife. 2015 Aug 12;4: [PMID: 26267217]
  50. Mol Syst Biol. 2021 Jul;17(7):e10127 [PMID: 34288498]
  51. Sci Rep. 2021 Apr 23;11(1):8828 [PMID: 33893325]
  52. FEBS Lett. 2020 May;594(10):1477-1496 [PMID: 32052437]
  53. Nature. 2010 Jul 8;466(7303):267-71 [PMID: 20581820]
  54. Nat Struct Mol Biol. 2011 Jul 17;18(8):956-63 [PMID: 21765417]
  55. Genome Biol. 2020 Feb 3;21(1):22 [PMID: 32014034]
  56. Mol Cell. 2021 Mar 4;81(5):969-982.e13 [PMID: 33482114]
  57. Mol Cell. 2014 Oct 23;56(2):219-231 [PMID: 25263595]
  58. Immunity. 2019 Mar 19;50(3):616-628.e6 [PMID: 30850343]
  59. J Immunol. 2004 Feb 15;172(4):2265-73 [PMID: 14764695]
  60. Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):E6437-E6446 [PMID: 29946020]
  61. Cell. 2017 Mar 23;169(1):13-23 [PMID: 28340338]
  62. Nat Genet. 2016 Dec 28;49(1):2-3 [PMID: 28029159]
  63. Biochemistry. 2002 May 28;41(21):6573-82 [PMID: 12022860]
  64. Cell Mol Immunol. 2012 Mar;9(2):123-30 [PMID: 22343828]

MeSH Term

Cell Nucleus
Gene Expression Regulation
NF-kappa B
Protein Binding
Regulatory Sequences, Nucleic Acid
Transcription Factor RelA
Transcriptional Activation

Chemicals

NF-kappa B
Transcription Factor RelA
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 16

Word Cloud

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