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FACT mediates cohesin function on chromatin

FACT mediates cohesin function on chromatin

来源:bioRxiv_logobioRxiv
英文摘要

Abstract Cohesin is a key regulator of genome architecture with roles in sister chromatid cohesion 1,2 and the organisation of higher-order structures during interphase 3 and mitosis 4,5. The recruitment and mobility of cohesin complexes on DNA is restricted by nucleosomes 6-8. Here we show that cohesin role in chromosome organisation requires the histone chaperone FACT. Depletion of FACT in metaphase cells affects cohesin stability on chromatin reducing its accumulation at pericentric regions and binding on chromosome arms. Using Hi-C, we show that cohesin-dependent TAD (Topological Associated Domains)-like structures in G1 and metaphase chromosomes are disrupted in the absence of FACT. Surprisingly, sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our results uncover a role for FACT in genome organisation by facilitating cohesin-dependent compartmentalization of chromosomes into loop domains.

Lazar-Stefanita Luciana、Garc¨aa Alicia、Jarmuz Adam、Dore Marian、Kramer Holger、Karimi Mohammad Mehdi、Antequera Francisco、Koszul Romain、Aragon Luis、Thierry Agnes、Gonz¨¢lez Sara、Gutierrez-Escribano Pilar、Garcia-Luis Jonay、Montoya Alex、S¨¢nchez Mar

Institut Pasteur, Department Genomes and Genetics, Unit¨| R¨|gulation Spatiale des G¨|nomesInstituto de Biolog¨aa Funcional y Gen¨?mica (IBFG), CSIC / Universidad de Salamanca, Zacar¨aas Gonz¨¢lezCell Cycle Group, MRC London Institute of Medical Sciences (LMS)Bioinformatics Facility, MRC London Institute of Medical Sciences (LMS)Biological Mass Spectrometry and Proteomics Facility, MRC London Institute of Medical Sciences (LMS)Bioinformatics Facility, MRC London Institute of Medical Sciences (LMS)Instituto de Biolog¨aa Funcional y Gen¨?mica (IBFG), CSIC / Universidad de Salamanca, Zacar¨aas Gonz¨¢lezInstitut Pasteur, Department Genomes and Genetics, Unit¨| R¨|gulation Spatiale des G¨|nomesCell Cycle Group, MRC London Institute of Medical Sciences (LMS)Institut Pasteur, Department Genomes and Genetics, Unit¨| R¨|gulation Spatiale des G¨|nomesInstituto de Biolog¨aa Funcional y Gen¨?mica (IBFG), CSIC / Universidad de Salamanca, Zacar¨aas Gonz¨¢lezCell Cycle Group, MRC London Institute of Medical Sciences (LMS)Cell Cycle Group, MRC London Institute of Medical Sciences (LMS)Biological Mass Spectrometry and Proteomics Facility, MRC London Institute of Medical Sciences (LMS)Instituto de Biolog¨aa Funcional y Gen¨?mica (IBFG), CSIC / Universidad de Salamanca, Zacar¨aas Gonz¨¢lez

10.1101/756601

分子生物学遗传学细胞生物学

Lazar-Stefanita Luciana,Garc¨aa Alicia,Jarmuz Adam,Dore Marian,Kramer Holger,Karimi Mohammad Mehdi,Antequera Francisco,Koszul Romain,Aragon Luis,Thierry Agnes,Gonz¨¢lez Sara,Gutierrez-Escribano Pilar,Garcia-Luis Jonay,Montoya Alex,S¨¢nchez Mar.FACT mediates cohesin function on chromatin[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/756601.点此复制

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