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Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation

  1. Author:
    Kieffer-Kwon, Kyong-Rim
    Nimura, Keisuke
    Rao, Suhas S P
    Xu, Jianliang
    Jung, Seolkyoung
    Pekowska, Aleksandra
    Dose, Marei
    Stevens, Evan
    Mathe, Ewy
    Dong, Peng
    Huang, Su-Chen
    Ricci, Maria Aurelia
    Baranello, Laura
    Zheng, Ying
    Tomassoni Ardori, Francesco
    Resch, Wolfgang
    Stavreva, Diana
    Nelson, Steevenson
    McAndrew, Michael
    Casellas, Adriel
    Finn, Elizabeth
    Gregory, Charles
    St Hilaire, Brian Glenn
    Johnson, Steven M
    Dubois, Wendy
    Cosma, Maria Pia
    Batchelor, Eric
    Levens, David
    Phair, Robert D
    Misteli, Tom
    Tessarollo, Lino
    Hager, Gordon
    Lakadamyali, Melike
    Liu, Zhe
    Floer, Monique
    Shroff, Hari
    Aiden, Erez Lieberman
    Casellas, Rafael
  2. Author Address

    Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., The Center for Genome Architecture, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA., Transcription Imaging Consortium, Janelia Farm Research Campus, HHMI, 19700 Helix Drive, Ashburn, VA 20147, USA., The Center for Genome Architecture, Baylor College of Medicine, Houston, Texas 77030, USA., ICFO-Institut de Ci 232;ncies Fot 242;niques, Barcelona Institute of Science and Technology, 08860 Castelldefels, Barcelona, Spain., Gene Regulation, Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA., Neural Development Section, Mouse Cancer Genetics Program, NCI, NIH, Frederick, MD 21702, USA., Laboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD 20892, USA., Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA., Section on High Resolution Optical Imaging, NIBIB, NIH, Bethesda, MD 20892, USA., Cell Biology of Genomes, NCI, NIH, Bethesda, MD 20892, USA., Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA., Center of Cancer Research, NCI, NIH, Bethesda, MD 20892, USA., Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Universitat Pompeu Fabra, Instituci 243; Catalana de Recerca i Estudis Avan 231;ats, Dr. Aiguader 88, Barcelona 08003, Spain., Systems Biology, Laboratory of Pathology, NCI, NIH, Bethesda, MD 20892, USA., Integrative Bioinformatics Inc., Mountain View, CA 94041, USA., The Center for Genome Architecture, Baylor College of Medicine, Houston, Texas 77030, USA. Electronic address: erez@erez.com., Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA; Center of Cancer Research, NCI, NIH, Bethesda, MD 20892, USA. Electronic address: rafael.casellas@nih.gov.,
    1. Year: 2017
    2. Date: Aug 17
    3. Epub Date: 2017 Jul 28
  1. Journal: Molecular Cell
    1. 67
    2. 4
    3. Pages: 566-578
  2. Type of Article: Article
  1. Abstract:

    50 years ago, Vincent Allfrey and colleagues discovered that lymphocyte activation triggers massive acetylation of chromatin. However, the molecular mechanisms driving epigenetic accessibility are still unknown. We here show that stimulated lymphocytes decondense chromatin by three differentially regulated steps. First, chromatin is repositioned away from the nuclear periphery in response to global acetylation. Second, histone nanodomain clusters decompact into mononucleosome fibers through a mechanism that requires Myc and continual energy input. Single-molecule imaging shows that this step lowers transcription factor residence time and non-specific collisions during sampling for DNA targets. Third, chromatin interactions shift from long range to predominantly short range, and CTCF-mediated loops and contact domains double in numbers. This architectural change facilitates cognate promoter-enhancer contacts and also requires Myc and continual ATP production. Our results thus define the nature and transcriptional impact of chromatin decondensation and reveal an unexpected role for Myc in the establishment of nuclear topology in mammalian cells. Published by Elsevier Inc.

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External Sources

  1. DOI: 10.1016/j.molcel.2017.07.013
  2. PMID: 28803781
  3. WOS: 000407935500004

Library Notes

  1. Fiscal Year: FY2016-2017
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