Polycomb-Dependent Chromatin Looping Contributes to Gene Silencing during Drosophila Development.

Abstract:

:Interphase chromatin is organized into topologically associating domains (TADs). Within TADs, chromatin looping interactions are formed between DNA regulatory elements, but their functional importance for the establishment of the 3D genome organization and gene regulation during development is unclear. Using high-resolution Hi-C experiments, we analyze higher order 3D chromatin organization during Drosophila embryogenesis and identify active and repressive chromatin loops that are established with different kinetics and depend on distinct factors: Zelda-dependent active loops are formed before the midblastula transition between transcribed genes over long distances. Repressive loops within polycomb domains are formed after the midblastula transition between polycomb response elements by the action of GAGA factor and polycomb proteins. Perturbation of PRE function by CRISPR/Cas9 genome engineering affects polycomb domain formation and destabilizes polycomb-mediated silencing. Preventing loop formation without removal of polycomb components also decreases silencing efficiency, suggesting that chromatin architecture can play instructive roles in gene regulation during development. VIDEO ABSTRACT.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Ogiyama Y,Schuettengruber B,Papadopoulos GL,Chang JM,Cavalli G

doi

10.1016/j.molcel.2018.05.032

subject

Has Abstract

pub_date

2018-07-05 00:00:00

pages

73-88.e5

issue

1

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(18)30407-6

journal_volume

71

pub_type

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