A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
Abstract: 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.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture ; volume:36 ; number:24 ; year:2017 ; pages:3600-3618 ; extent:19
The EMBO journal / European Molecular Biology Organization ; 36, Heft 24 (2017), 3600-3618 (gesamt 19)
- Urheber
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Gassler, Johanna
Brandão, Hugo B.
Imakaev, Maxim
Flyamer, Ilya M.
Ladstätter, Sabrina
Bickmore, Wendy A.
Peters, Jan-Michael
Mirny, Leonid A.
Tachibana, Kikuë
- DOI
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10.15252/embj.201798083
- URN
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urn:nbn:de:101:1-2022100306420178113446
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:25 MESZ
Datenpartner
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Beteiligte
- Gassler, Johanna
- Brandão, Hugo B.
- Imakaev, Maxim
- Flyamer, Ilya M.
- Ladstätter, Sabrina
- Bickmore, Wendy A.
- Peters, Jan-Michael
- Mirny, Leonid A.
- Tachibana, Kikuë
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