The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension
| Autor: | Lattanzi, Annalisa, Meneghini, Vasco, Pavani, Giulia, Amor, Fatima, Ramadier, Sophie, Felix, Tristan, Antoniani, Chiara, Masson, Cecile, Alibeu, Olivier, Lee, Ciaran, Porteus, Matthew, Bao, Gang, Mavilio, Fulvio, Miccio, Annarita, Romano, Oriana, Magrin, Elisa, Weber, Leslie, El Hoss, Sara, Kurita, Ryo, Nakamura, Yukio, Cradick, Thomas, Lundberg, Ante, El Nemer, Wassim, Cavazzana, Marina, Haarhuis, Judith H.I., van Der Weide, Robin, Blomen, Vincent, Yáñez-Cuna, J. Omar, Amendola, Mario, van Ruiten, Marjon, Krijger, Peter H.L., Teunissen, Hans, Medema, René, van Steensel, Bas, Brummelkamp, Thijn, de Wit, Elzo, Rowland, Benjamin |
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| Přispěvatelé: | Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Généthon |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CCCTC-Binding Factor [SDV.BIO]Life Sciences [q-bio]/Biotechnology Chromosomal Proteins Non-Histone cohesin Cell Cycle Proteins Biochemistry NIPBL SCC2 chemistry.chemical_compound 0302 clinical medicine SCC4 chromatin looping Gene Editing Genetics loop extrusion Nuclear Proteins [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology Chromatin Cell biology DNA-Binding Proteins medicine.anatomical_structure WAPL Chromatin Loop biological phenomena cell phenomena and immunity Release factor Cohesin complex Fatty Acid Elongases [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Acetyltransferases Proto-Oncogene Proteins medicine Journal Article Humans TADs Cell Nucleus Cohesin Biochemistry Genetics and Molecular Biology(all) CTCF MAU2 Repressor Proteins Cell nucleus 030104 developmental biology chemistry Multiprotein Complexes Carrier Proteins 030217 neurology & neurosurgery DNA Genetics and Molecular Biology(all) |
| Zdroj: | Cell, 169(4), 693. Cell Press Cell Cell, 2017, 169 (4), pp.693-707.e14. ⟨10.1016/j.cell.2017.04.013⟩ |
| ISSN: | 0092-8674 1097-4172 |
| DOI: | 10.1016/j.cell.2017.04.013⟩ |
| Popis: | Summary The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin’s DNA release factor WAPL restricts this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes. Graphical Abstract Highlights • Hi-C analysis demonstrates that chromatin loop size can be increased genome-wide • The duration with which cohesin embraces DNA determines the length of chromatin loops • Haploid genetics reveals that the SCC2/SCC4 complex promotes loop extension • Cohesin limits the compartmentalization of chromatin within the nucleus Cohesin's dynamic association with DNA determines the length of chromatin loops and allows this complex to correctly structure chromosomes. |
| Databáze: | OpenAIRE |
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