A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
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A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
Machine scores (provisional)
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
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- Teacher spread
- 0.214 · how far apart the two teachers sit on this one work
- Validation status
score_only:v0-immature-baseline· verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it
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.
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The record
- Venue
- The EMBO Journal
- Topic
- Genomics and Chromatin Dynamics
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- —
- Funders
- National Institute of Diabetes and Digestive and Kidney DiseasesNatural Sciences and Engineering Research Council of CanadaAustrian Science FundDarwin Trust of EdinburghNational Institute of General Medical SciencesMedical Research CouncilÖsterreichischen Akademie der WissenschaftenWellcome TrustEuropean Research CouncilNational Institutes of HealthNational Science Foundation
- Keywords
- CohesinChromatinBiologyZygoteProcessivityCell biologyGeneticsGenomeMaternal to zygotic transitionEpigeneticsEmbryoCTCFDNADNA replicationEnhancerEmbryogenesisGeneGene expression
- Has abstract in OpenAlex
- yes