PMID- 31582854 OWN - NLM STAT- MEDLINE DCOM- 20200211 LR - 20231213 IS - 1545-9985 (Electronic) IS - 1545-9993 (Print) IS - 1545-9985 (Linking) VI - 26 IP - 10 DP - 2019 Oct TI - FACT mediates cohesin function on chromatin. PG - 970-979 LID - 10.1038/s41594-019-0307-x [doi] AB - Cohesin is a regulator of genome architecture with roles in sister chromatid cohesion and chromosome compaction. The recruitment and mobility of cohesin complexes on DNA is restricted by nucleosomes. Here, we show that the role of cohesin in chromosome organization requires the histone chaperone FACT ('facilitates chromatin transcription') in Saccharomyces cerevisiae. We find that FACT interacts directly with cohesin, and is dynamically required for its localization on chromatin. Depletion of FACT in metaphase cells prevents cohesin accumulation at pericentric regions and causes reduced binding on chromosome arms. Using the Hi-C technique, we show that cohesin-dependent TAD (topological associated domain)-like structures in G1 and metaphase chromosomes are reduced in the absence of FACT. Sister chromatid cohesion is intact in FACT-depleted cells, although chromosome segregation failure is observed. Our data show that FACT contributes to the formation of cohesin-dependent TADs, thus uncovering a new role for this complex in nuclear organization during interphase and mitotic chromosome folding. FAU - Garcia-Luis, Jonay AU - Garcia-Luis J AD - Cell Cycle Group, MRC London Institute of Medical Sciences (LMS), London, UK. FAU - Lazar-Stefanita, Luciana AU - Lazar-Stefanita L AD - Institut Pasteur, Department of Genomes and Genetics, Unite Regulation Spatiale des Genomes, Paris, France. FAU - Gutierrez-Escribano, Pilar AU - Gutierrez-Escribano P AD - Cell Cycle Group, MRC London Institute of Medical Sciences (LMS), London, UK. FAU - Thierry, Agnes AU - Thierry A AD - Institut Pasteur, Department of Genomes and Genetics, Unite Regulation Spatiale des Genomes, Paris, France. FAU - Cournac, Axel AU - Cournac A AD - Institut Pasteur, Department of Genomes and Genetics, Unite Regulation Spatiale des Genomes, Paris, France. FAU - Garcia, Alicia AU - Garcia A AD - Instituto de Biologia Funcional y Genomica (IBFG), CSIC/Universidad de Salamanca, Salamanca, Spain. FAU - Gonzalez, Sara AU - Gonzalez S AD - Instituto de Biologia Funcional y Genomica (IBFG), CSIC/Universidad de Salamanca, Salamanca, Spain. FAU - Sanchez, Mar AU - Sanchez M AD - Instituto de Biologia Funcional y Genomica (IBFG), CSIC/Universidad de Salamanca, Salamanca, Spain. FAU - Jarmuz, Adam AU - Jarmuz A AD - Cell Cycle Group, MRC London Institute of Medical Sciences (LMS), London, UK. FAU - Montoya, Alex AU - Montoya A AD - Biological Mass Spectrometry and Proteomics Facility, MRC London Institute of Medical Sciences (LMS), London, UK. FAU - Dore, Marian AU - Dore M AD - Bioinformatics Facility, MRC London Institute of Medical Sciences (LMS), London, UK. FAU - Kramer, Holger AU - Kramer H AD - Biological Mass Spectrometry and Proteomics Facility, MRC London Institute of Medical Sciences (LMS), London, UK. FAU - Karimi, Mohammad M AU - Karimi MM AUID- ORCID: 0000-0001-5017-1252 AD - Bioinformatics Facility, MRC London Institute of Medical Sciences (LMS), London, UK. FAU - Antequera, Francisco AU - Antequera F AD - Instituto de Biologia Funcional y Genomica (IBFG), CSIC/Universidad de Salamanca, Salamanca, Spain. FAU - Koszul, Romain AU - Koszul R AUID- ORCID: 0000-0002-3086-1173 AD - Institut Pasteur, Department of Genomes and Genetics, Unite Regulation Spatiale des Genomes, Paris, France. romain.koszul@pasteur.fr. FAU - Aragon, Luis AU - Aragon L AUID- ORCID: 0000-0003-0634-6742 AD - Cell Cycle Group, MRC London Institute of Medical Sciences (LMS), London, UK. luis.aragon@csc.mrc.ac.uk. LA - eng GR - Wellcome Trust/United Kingdom GR - 100955/Wellcome Trust/United Kingdom GR - MC_U120074328/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191003 PL - United States TA - Nat Struct Mol Biol JT - Nature structural & molecular biology JID - 101186374 RN - 0 (Cell Cycle Proteins) RN - 0 (Chromatin) RN - 0 (Chromosomal Proteins, Non-Histone) RN - 0 (DNA-Binding Proteins) RN - 0 (FACT protein, S cerevisiae) RN - 0 (High Mobility Group Proteins) RN - 0 (SPT16 protein, S cerevisiae) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 0 (Transcriptional Elongation Factors) RN - 0 (structural maintenance of chromosome protein 1) SB - IM MH - Cell Cycle Proteins/*metabolism MH - Chromatin/metabolism MH - Chromosomal Proteins, Non-Histone/*metabolism MH - DNA-Binding Proteins/metabolism MH - High Mobility Group Proteins/metabolism MH - Protein Interaction Maps MH - Saccharomyces cerevisiae/cytology/*metabolism MH - Saccharomyces cerevisiae Proteins/*metabolism MH - Transcriptional Elongation Factors/*metabolism MH - Cohesins PMC - PMC6779571 MID - EMS84179 COIS- Competing interests The authors declare no competing interests. EDAT- 2019/10/05 06:00 MHDA- 2020/02/12 06:00 PMCR- 2020/04/03 CRDT- 2019/10/05 06:00 PHST- 2019/06/18 00:00 [received] PHST- 2019/08/21 00:00 [accepted] PHST- 2019/10/05 06:00 [entrez] PHST- 2019/10/05 06:00 [pubmed] PHST- 2020/02/12 06:00 [medline] PHST- 2020/04/03 00:00 [pmc-release] AID - 10.1038/s41594-019-0307-x [pii] AID - 10.1038/s41594-019-0307-x [doi] PST - ppublish SO - Nat Struct Mol Biol. 2019 Oct;26(10):970-979. doi: 10.1038/s41594-019-0307-x. Epub 2019 Oct 3.