Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation.
Autor: | Kieffer-Kwon KR; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Nimura K; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Rao SSP; 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., Xu J; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Jung S; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Pekowska A; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Dose M; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Stevens E; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Mathe E; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Dong P; Transcription Imaging Consortium, Janelia Farm Research Campus, HHMI, 19700 Helix Drive, Ashburn, VA 20147, USA., Huang SC; The Center for Genome Architecture, Baylor College of Medicine, Houston, Texas 77030, USA., Ricci MA; ICFO-Institut de Ciències Fotòniques, Barcelona Institute of Science and Technology, 08860 Castelldefels, Barcelona, Spain., Baranello L; Gene Regulation, Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA., Zheng Y; Gene Regulation, Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA., Tomassoni Ardori F; Neural Development Section, Mouse Cancer Genetics Program, NCI, NIH, Frederick, MD 21702, USA., Resch W; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Stavreva D; Laboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD 20892, USA., Nelson S; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., McAndrew M; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA., Casellas A; Section on High Resolution Optical Imaging, NIBIB, NIH, Bethesda, MD 20892, USA., Finn E; Cell Biology of Genomes, NCI, NIH, Bethesda, MD 20892, USA., Gregory C; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., St Hilaire BG; The Center for Genome Architecture, Baylor College of Medicine, Houston, Texas 77030, USA., Johnson SM; Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA., Dubois W; Center of Cancer Research, NCI, NIH, Bethesda, MD 20892, USA., Cosma MP; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Universitat Pompeu Fabra, Institució Catalana de Recerca i Estudis Avançats, Dr. Aiguader 88, Barcelona 08003, Spain., Batchelor E; Systems Biology, Laboratory of Pathology, NCI, NIH, Bethesda, MD 20892, USA., Levens D; Gene Regulation, Laboratory of Pathology, Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA., Phair RD; Integrative Bioinformatics Inc., Mountain View, CA 94041, USA., Misteli T; Cell Biology of Genomes, NCI, NIH, Bethesda, MD 20892, USA., Tessarollo L; Neural Development Section, Mouse Cancer Genetics Program, NCI, NIH, Frederick, MD 21702, USA., Hager G; Laboratory of Receptor Biology and Gene Expression, NCI, NIH, Bethesda, MD 20892, USA., Lakadamyali M; ICFO-Institut de Ciències Fotòniques, Barcelona Institute of Science and Technology, 08860 Castelldefels, Barcelona, Spain., Liu Z; Transcription Imaging Consortium, Janelia Farm Research Campus, HHMI, 19700 Helix Drive, Ashburn, VA 20147, USA., Floer M; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA., Shroff H; Section on High Resolution Optical Imaging, NIBIB, NIH, Bethesda, MD 20892, USA., Aiden EL; The Center for Genome Architecture, Baylor College of Medicine, Houston, Texas 77030, USA. Electronic address: erez@erez.com., Casellas R; 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. |
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Jazyk: | angličtina |
Zdroj: | Molecular cell [Mol Cell] 2017 Aug 17; Vol. 67 (4), pp. 566-578.e10. Date of Electronic Publication: 2017 Aug 10. |
DOI: | 10.1016/j.molcel.2017.07.013 |
Abstrakt: | 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.) |
Databáze: | MEDLINE |
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