Pubblicazione scientifica

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

FILONE TECNOLOGICO	TEMA
produzione e cattura

RIASSUNTO

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.

DATA

Data di pubblicazione: 07/12/2017

AUTORI

GASSLER JOHANNA
BRANDAO HUGO B
IMAKAEV MAXIM
FLYAMER ILYA M
LADSTATTER SABRINA
BICKMORE WENDY A
PETERS JAN‐MICHAEL
MIRNY LEONID A
TACHIBANA KIKUE

ENTE DI AFFERENZA

INST MOLECULAR BIOTECHNOLOGY AUSTRIAN ACAD SCIENCES IMBA VIENNA BIOCENTER VBC VIENNA AUSTRIA
HARVARD GRADUATE PROGRAM IN BIOPHYSICS HARVARD UNIV CAMBRIDGE MA USA
INST MEDICAL ENG & SCIENCE MASSACHUSETTS INST TECH MIT CAMBRIDGE MA USA
DEPT PHYSICS MASSACHUSETTS INST TECH MIT CAMBRIDGE MA USA
MRC HUMAN GENETICS UNIT INST GENETICS & MOLECULAR MEDICINE UNIV EDINBURGH EDINBURGH UK
RESEARCH INST MOLECULAR PATHOLOGY IMP VIENNA BIOCENTER VBC VIENNA AUSTRIA

RIVISTA

The EMBO Journal, 36(24), 3600-3618

indietro