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The Energetics and Physiological Impact of Cohesin Extrusion.
Vian, Laura; Pekowska, Aleksandra; Rao, Suhas S P; Kieffer-Kwon, Kyong-Rim; Jung, Seolkyoung; Baranello, Laura; Huang, Su-Chen; El Khattabi, Laila; Dose, Marei; Pruett, Nathanael; Sanborn, Adrian L; Canela, Andres; Maman, Yaakov; Oksanen, Anna; Resch, Wolfgang; Li, Xingwang; Lee, Byoungkoo; Kovalchuk, Alexander L; Tang, Zhonghui; Nelson, Steevenson; Di Pierro, Michele; Cheng, Ryan R; Machol, Ido; St Hilaire, Brian Glenn; Durand, Neva C; Shamim, Muhammad S; Stamenova, Elena K; Onuchic, José N; Ruan, Yijun; Nussenzweig, Andre; Levens, David; Aiden, Erez Lieberman; Casellas, Rafael.
Afiliação
  • Vian L; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Pekowska A; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Rao SSP; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • Kieffer-Kwon KR; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Jung S; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Baranello L; Gene Regulation, Laboratory of Pathology, NCI, NIH, Bethesda, MD 20892, USA.
  • Huang SC; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA.
  • El Khattabi L; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Dose M; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Pruett N; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Sanborn AL; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
  • Canela A; Laboratory of Genome Integrity, NCI, NIH, Bethesda, MD 20892, USA.
  • Maman Y; Laboratory of Genome Integrity, NCI, NIH, Bethesda, MD 20892, USA.
  • Oksanen A; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Resch W; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Li X; The Jackson Laboratory for Genomic Medicine and Department of Genetic and Development Biology, University of Connecticut, Farmington, CT 06030, USA.
  • Lee B; The Jackson Laboratory for Genomic Medicine and Department of Genetic and Development Biology, University of Connecticut, Farmington, CT 06030, USA.
  • Kovalchuk AL; Laboratory of Immunogenetics, NIAID, NIH, Rockville, MD 20852, USA.
  • Tang Z; The Jackson Laboratory for Genomic Medicine and Department of Genetic and Development Biology, University of Connecticut, Farmington, CT 06030, USA.
  • Nelson S; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
  • Di Pierro M; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA.
  • Cheng RR; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA.
  • Machol I; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA.
  • St Hilaire BG; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA.
  • Durand NC; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA.
  • Shamim MS; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA.
  • Stamenova EK; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA.
  • Onuchic JN; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA.
  • Ruan Y; The Jackson Laboratory for Genomic Medicine and Department of Genetic and Development Biology, University of Connecticut, Farmington, CT 06030, USA.
  • Nussenzweig A; Laboratory of Genome Integrity, NCI, NIH, Bethesda, MD 20892, USA.
  • Levens D; Gene Regulation, Laboratory of Pathology, NCI, NIH, Bethesda, MD 20892, USA.
  • Aiden EL; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China. Electronic address: erez@erez.
  • 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.
Cell ; 173(5): 1165-1178.e20, 2018 05 17.
Article em En | MEDLINE | ID: mdl-29706548
ABSTRACT
Cohesin extrusion is thought to play a central role in establishing the architecture of mammalian genomes. However, extrusion has not been visualized in vivo, and thus, its functional impact and energetics are unknown. Using ultra-deep Hi-C, we show that loop domains form by a process that requires cohesin ATPases. Once formed, however, loops and compartments are maintained for hours without energy input. Strikingly, without ATP, we observe the emergence of hundreds of CTCF-independent loops that link regulatory DNA. We also identify architectural "stripes," where a loop anchor interacts with entire domains at high frequency. Stripes often tether super-enhancers to cognate promoters, and in B cells, they facilitate Igh transcription and recombination. Stripe anchors represent major hotspots for topoisomerase-mediated lesions, which promote chromosomal translocations and cancer. In plasmacytomas, stripes can deregulate Igh-translocated oncogenes. We propose that higher organisms have coopted cohesin extrusion to enhance transcription and recombination, with implications for tumor development.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Cromossômicas não Histona / Trifosfato de Adenosina / Genoma / Proteínas de Ciclo Celular Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Cromossômicas não Histona / Trifosfato de Adenosina / Genoma / Proteínas de Ciclo Celular Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article