ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL

Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin’s chromatin residence time to minutes, it has been reported tha...

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Published ineLife Vol. 9
Main Authors Wutz, Gordana, Ladurner, Rene, St Hilaire, Brian Glenn, Stocsits, Roman R, Nagasaka, Kota, Pignard, Benoit, Sanborn, Adrian, Tang, Wen, Várnai, Csilla, Ivanov, Miroslav P, Schoenfelder, Stefan, van der Lelij, Petra, Huang, Xingfan, Dürnberger, Gerhard, Roitinger, Elisabeth, Mechtler, Karl, Davidson, Iain Finley, Fraser, Peter, Lieberman-Aiden, Erez, Peters, Jan-Michael
Format Journal Article
LanguageEnglish
Published Cambridge eLife Sciences Publications Ltd 17.02.2020
eLife Sciences Publications, Ltd
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Online AccessGet full text
ISSN2050-084X
2050-084X
DOI10.7554/eLife.52091

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Abstract Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin’s chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesinSTAG1 which binds chromatin for hours, whereas cohesinSTAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesinSTAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesinSTAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesinSTAG2 extrusion activity.
AbstractList Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin’s chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesinSTAG1 which binds chromatin for hours, whereas cohesinSTAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesinSTAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesinSTAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesinSTAG2 extrusion activity.
Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin's chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesinSTAG1 which binds chromatin for hours, whereas cohesinSTAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesinSTAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesinSTAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesinSTAG2 extrusion activity.Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin's chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesinSTAG1 which binds chromatin for hours, whereas cohesinSTAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesinSTAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesinSTAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesinSTAG2 extrusion activity.
Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin’s chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesin STAG1 which binds chromatin for hours, whereas cohesin STAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesin STAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesin STAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesin STAG2 extrusion activity.
Author Roitinger, Elisabeth
Mechtler, Karl
Peters, Jan-Michael
Nagasaka, Kota
Ivanov, Miroslav P
Várnai, Csilla
Dürnberger, Gerhard
Ladurner, Rene
Schoenfelder, Stefan
Fraser, Peter
Tang, Wen
Huang, Xingfan
Davidson, Iain Finley
Wutz, Gordana
Sanborn, Adrian
van der Lelij, Petra
St Hilaire, Brian Glenn
Stocsits, Roman R
Lieberman-Aiden, Erez
Pignard, Benoit
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2020, Wutz et al.
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The Francis Crick Institute, London, United Kingdom.
Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom.
Gregor Mendel Institute of Molecular Plant Biology Austrian Academy of Sciences, Vienna, Austria.
Department of Biochemistry, Stanford University School of Medicine, Stanford, United States.
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0000-0002-3200-8133
0000-0003-0765-638X
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Snippet Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by...
Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by...
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SubjectTerms Acetyltransferase
Cell Biology
Cell cycle
Chromatin
chromatin structure
Chromosomes
Chromosomes and Gene Expression
Cohesin
CTCF
Deoxyribonucleic acid
DNA
Experiments
genome organization
Genomes
Hypotheses
loops
Mammalian cells
Proteins
TADs
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Title ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL
URI https://www.proquest.com/docview/2384741761
https://www.proquest.com/docview/2356589050
https://pubmed.ncbi.nlm.nih.gov/PMC7054000
https://doaj.org/article/50f9b518193c4de2ba8e04afd984547d
Volume 9
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