Cohesin catalyses the folding of the genome into loops that are anchored by CTCF1. The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2-SCC1 subunits of human cohesin. We report a crystal structure of SA2-SCC1 in complex with CTCF at a resolution of 2.7 angstrom, which reveals the molecular basis of the interaction. We demonstrate that this interaction is specifically required for CTCF-anchored loops and contributes to the positioning of cohesin at CTCF binding sites. A similar motif is present in a number of established and newly identified cohesin ligands, including the cohesin release factor WAPL(2,3). Our data suggest that CTCF enables the formation of chromatin loops by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables the dynamic regulation of chromatin folding by cohesin and CTCF. The crystal structure of the SA2-SCC1 subunits of human cohesin in complex with CTCF reveals the molecular basis of the cohesin-CTCF interaction that enables the dynamic regulation of chromatin folding.
机构:
Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Austrian Acad Sci IMBA, Vienna Bioctr VBC, Inst Mol Biotechnol, Vienna, Austria
Austrian Acad Sci, Vienna Bioctr VBC, Gregor Mendel Inst, Vienna, Austria
Tech Res & Dev Novartis, Kundl, AustriaVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Holzmann, Johann
Politi, Antonio Z.
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EMBL, Cell Biol & Biophys Unit, Heidelberg, Germany
Max Planck Inst Biophys Chem, Gottingen, GermanyVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Politi, Antonio Z.
Nagasaka, Kota
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机构:
Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, AustriaVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Nagasaka, Kota
Hantsche-Grininger, Merle
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EMBL, Cell Biol & Biophys Unit, Heidelberg, GermanyVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Hantsche-Grininger, Merle
Walther, Nike
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机构:
EMBL, Cell Biol & Biophys Unit, Heidelberg, Germany
Univ Calif Berkeley, Dept Mol & Cell Biol, Li Ka Shing Ctr Biomed & Hlth Sci, CIRM Ctr Excellence, 229 Stanley Hall, Berkeley, CA 94720 USAVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Walther, Nike
Koch, Birgit
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EMBL, Cell Biol & Biophys Unit, Heidelberg, Germany
Univ Gothenburg, Prote Core Facil, Gothenburg, SwedenVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Koch, Birgit
Fuchs, Johannes
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h-index: 0
机构:
Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Austrian Acad Sci IMBA, Vienna Bioctr VBC, Inst Mol Biotechnol, Vienna, Austria
Austrian Acad Sci, Vienna Bioctr VBC, Gregor Mendel Inst, Vienna, Austria
Stanford Univ, Dept Biochem, Stanford, CA 94305 USAVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Fuchs, Johannes
Duernberger, Gerhard
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Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Austrian Acad Sci IMBA, Vienna Bioctr VBC, Inst Mol Biotechnol, Vienna, Austria
Austrian Acad Sci, Vienna Bioctr VBC, Gregor Mendel Inst, Vienna, AustriaVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Duernberger, Gerhard
Tang, Wen
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Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, AustriaVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Tang, Wen
Ladurner, Rene
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Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Univ Med Ctr Utrecht, Royal Netherlands Acad Arts & Sci, Hubrecht Inst, Utrecht, NetherlandsVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Ladurner, Rene
Stocsits, Roman R.
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机构:
Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, AustriaVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Stocsits, Roman R.
Busslinger, Georg A.
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Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, AustriaVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Busslinger, Georg A.
Novak, Bela
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Univ Oxford, Dept Biochem, Oxford, EnglandVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Novak, Bela
Mechtler, Karl
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机构:
Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Austrian Acad Sci IMBA, Vienna Bioctr VBC, Inst Mol Biotechnol, Vienna, Austria
Austrian Acad Sci, Vienna Bioctr VBC, Gregor Mendel Inst, Vienna, AustriaVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Mechtler, Karl
Davidson, Iain Finley
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Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, AustriaVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Davidson, Iain Finley
Ellenberg, Jan
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EMBL, Cell Biol & Biophys Unit, Heidelberg, GermanyVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Ellenberg, Jan
Peters, Jan-Michael
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机构:
Vienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
Med Univ Vienna, Vienna, AustriaVienna Bioctr VBC, Res Inst Mol Pathol IMP, Vienna, Austria
机构:
Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Lymphocyte Dev Grp, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Lymphocyte Dev Grp, London W12 0NN, England
Seitan, Vlad C.
Krangel, Michael S.
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机构:
Duke Univ, Med Ctr, Dept Immunol, Durham, NC USAUniv London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Lymphocyte Dev Grp, London W12 0NN, England
Krangel, Michael S.
Merkenschlager, Matthias
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Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Lymphocyte Dev Grp, London W12 0NN, EnglandUniv London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Lymphocyte Dev Grp, London W12 0NN, England