A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture
Name
embj.201798083.pdf
Description
Published version
Size
3.31 MB
Format
Adobe PDF
Checksum (MD5)
56c74a9f16819dd0296898e5acf3017d
Author(s)
Imakaev, Maksim Viktorovich
Mirny, Leonid A
Date Issued
December 2017
Journal
The EMBO journal
Publisher
EMBO
Citation
Gassler, Johanna et al. “A mechanism of cohesin‐dependent loop extrusion organizes zygotic genome architecture.” The EMBO journal, vol. 36, no. 24, 2017, pp. 3600–3618 © 2017 The Author(s)
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.15252/EMBJ.201798083
