Cohesin Loss Eliminates All Loop Domains.

Autor:	Rao SSP; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA., Huang SC; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Glenn St Hilaire B; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA., Engreitz JM; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA., Perez EM; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA., Kieffer-Kwon KR; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA., Sanborn AL; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA., Johnstone SE; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Bascom GD; Department of Chemistry, New York University, New York, NY 10003, USA., Bochkov ID; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Huang X; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Departments of Computer Science and Computational and Applied Mathematics, Rice University, Houston, TX 77030, USA., Shamim MS; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Departments of Computer Science and Computational and Applied Mathematics, Rice University, Houston, TX 77030, USA; Medical Scientist Training Program, Baylor College of Medicine, Houston, TX 77030, USA., Shin J; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Departments of Computer Science and Computational and Applied Mathematics, Rice University, Houston, TX 77030, USA., Turner D; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA., Ye Z; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Departments of Computer Science and Computational and Applied Mathematics, Rice University, Houston, TX 77030, USA., Omer AD; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Robinson JT; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA., Schlick T; Department of Chemistry, New York University, New York, NY 10003, USA; Courant Institute of Mathematical Sciences, New York University, New York, NY 10012, USA; NYU-ECNU Center for Computational Chemistry, NYU Shanghai, Shanghai 200062, China., Bernstein BE; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA., Casellas R; Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA; Center of Cancer Research, NCI, NIH, Bethesda, MD 20892, USA., Lander ES; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Department of Biology, MIT, Cambridge, MA 02139, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA., Aiden EL; The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Center for Theoretical Biological Physics, Rice University, Houston, TX 77030, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02139, USA; Departments of Computer Science and Computational and Applied Mathematics, Rice University, Houston, TX 77030, USA. Electronic address: erez@erez.com.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2017 Oct 05; Vol. 171 (2), pp. 305-320.e24.
DOI:	10.1016/j.cell.2017.09.026
Abstrakt:	The human genome folds to create thousands of intervals, called "contact domains," that exhibit enhanced contact frequency within themselves. "Loop domains" form because of tethering between two loci-almost always bound by CTCF and cohesin-lying on the same chromosome. "Compartment domains" form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation of each loop. Although re-formation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid. (Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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