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A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture

Fertilization triggers assembly of higher‐order chromatin structure from a condensed maternal and a naïve paternal genome to generate a totipotent embryo. Chromatin loops and domains have been detected in mouse zygotes by single‐nucleus Hi‐C (snHi‐C), but not bulk Hi‐C. It is therefore unclear when...

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Autores principales: Gassler, Johanna, Brandão, Hugo B, Imakaev, Maxim, Flyamer, Ilya M, Ladstätter, Sabrina, Bickmore, Wendy A, Peters, Jan‐Michael, Mirny, Leonid A, Tachibana, Kikuë
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730859/
https://www.ncbi.nlm.nih.gov/pubmed/29217590
http://dx.doi.org/10.15252/embj.201798083
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author Gassler, Johanna
Brandão, Hugo B
Imakaev, Maxim
Flyamer, Ilya M
Ladstätter, Sabrina
Bickmore, Wendy A
Peters, Jan‐Michael
Mirny, Leonid A
Tachibana, Kikuë
author_facet Gassler, Johanna
Brandão, Hugo B
Imakaev, Maxim
Flyamer, Ilya M
Ladstätter, Sabrina
Bickmore, Wendy A
Peters, Jan‐Michael
Mirny, Leonid A
Tachibana, Kikuë
author_sort Gassler, Johanna
collection PubMed
description Fertilization triggers assembly of higher‐order chromatin structure from a condensed maternal and a naïve paternal genome to generate a totipotent embryo. Chromatin loops and domains have been detected in mouse zygotes by single‐nucleus Hi‐C (snHi‐C), but not bulk Hi‐C. It is therefore unclear when and how embryonic chromatin conformations are assembled. Here, we investigated whether a mechanism of cohesin‐dependent loop extrusion generates higher‐order chromatin structures within the one‐cell embryo. Using snHi‐C of mouse knockout embryos, we demonstrate that the zygotic genome folds into loops and domains that critically depend on Scc1‐cohesin and that are regulated in size and linear density by Wapl. Remarkably, we discovered distinct effects on maternal and paternal chromatin loop sizes, likely reflecting differences in loop extrusion dynamics and epigenetic reprogramming. Dynamic polymer models of chromosomes reproduce changes in snHi‐C, suggesting a mechanism where cohesin locally compacts chromatin by active loop extrusion, whose processivity is controlled by Wapl. Our simulations and experimental data provide evidence that cohesin‐dependent loop extrusion organizes mammalian genomes over multiple scales from the one‐cell embryo onward.
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spelling pubmed-57308592017-12-18 A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture Gassler, Johanna Brandão, Hugo B Imakaev, Maxim Flyamer, Ilya M Ladstätter, Sabrina Bickmore, Wendy A Peters, Jan‐Michael Mirny, Leonid A Tachibana, Kikuë EMBO J Articles Fertilization triggers assembly of higher‐order chromatin structure from a condensed maternal and a naïve paternal genome to generate a totipotent embryo. Chromatin loops and domains have been detected in mouse zygotes by single‐nucleus Hi‐C (snHi‐C), but not bulk Hi‐C. It is therefore unclear when and how embryonic chromatin conformations are assembled. Here, we investigated whether a mechanism of cohesin‐dependent loop extrusion generates higher‐order chromatin structures within the one‐cell embryo. Using snHi‐C of mouse knockout embryos, we demonstrate that the zygotic genome folds into loops and domains that critically depend on Scc1‐cohesin and that are regulated in size and linear density by Wapl. Remarkably, we discovered distinct effects on maternal and paternal chromatin loop sizes, likely reflecting differences in loop extrusion dynamics and epigenetic reprogramming. Dynamic polymer models of chromosomes reproduce changes in snHi‐C, suggesting a mechanism where cohesin locally compacts chromatin by active loop extrusion, whose processivity is controlled by Wapl. Our simulations and experimental data provide evidence that cohesin‐dependent loop extrusion organizes mammalian genomes over multiple scales from the one‐cell embryo onward. John Wiley and Sons Inc. 2017-12-07 2017-12-15 /pmc/articles/PMC5730859/ /pubmed/29217590 http://dx.doi.org/10.15252/embj.201798083 Text en © 2017 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the Creative Commons Attribution 4.0 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Articles
Gassler, Johanna
Brandão, Hugo B
Imakaev, Maxim
Flyamer, Ilya M
Ladstätter, Sabrina
Bickmore, Wendy A
Peters, Jan‐Michael
Mirny, Leonid A
Tachibana, Kikuë
A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
title A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
title_full A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
title_fullStr A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
title_full_unstemmed A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
title_short A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
title_sort mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5730859/
https://www.ncbi.nlm.nih.gov/pubmed/29217590
http://dx.doi.org/10.15252/embj.201798083
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