TADs: Dynamic structures to create stable regulatory functions |
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| Affiliation: | 1. Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-0054, Japan;2. School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, 226-8501, Japan;3. Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, 226-8503, Japan;1. Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark;2. The Finsen Laboratory, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark;3. Department of Urology, Charité-Universitätsmedizin Berlin, Berlin, Germany;4. Berlin Institute of Health at Charité - Universitätsmedizin, BIH Center for Regenerative Therapies, Berlin, Germany;5. Max-Planck Institute for Molecular Genetics, Berlin, Germany;1. Department of Chemistry, New York University, 100 Washington Square East, Silver Building, New York, 10003, NY, USA;2. Courant Institute of Mathematical Sciences, New York University, 251 Mercer St., New York, 10012, NY, USA;3. New York University-East China Normal University Center for Computational Chemistry, New York University Shanghai, Room 340, Geography Building, 3663 North Zhongshan Road, Shanghai, 200122, China;4. Simons Center for Computational Physical Chemistry, New York University, 24 Waverly Place, Silver Building, New York, NY, 10003, USA;1. Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA;2. Integrative Nuclear Architecture Laboratory, Center for Human Technologies, Istituto Italiano di Tecnologia, Genova, Italy;1. Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Campus-Vienna-Biocenter 1, Vienna 1030, Austria;2. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna Biocenter (VBC), Dr. Bohr-Gasse 3, Vienna 1030, Austria;3. Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, Vienna 1030, Austria |
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| Abstract: | Mammalian chromosomes are organized at different length scales within the cell nucleus. Topologically Associating Domains (TADs) are structural units of 3D genome organization with functions in gene regulation, DNA replication, recombination and repair. Whereas TADs were initially interpreted as insulated domains, recent studies are revealing that these domains should be interpreted as dynamic collections of actively extruding loops. This process of loop extrusion is subsequently blocked at dedicated TAD boundaries, thereby promoting intra-domain interactions over their surroundings. In this review, we discuss how mammalian TAD structure can emerge from this dynamic process and we discuss recent evidence that TAD boundaries can have regulatory functions. |
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| Keywords: | TADs Cohesin CTCF Enhancer-promoter looping Loop extrusion |
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