Format

Send to

Choose Destination
Mol Cell. 2018 Jul 5;71(1):73-88.e5. doi: 10.1016/j.molcel.2018.05.032. Epub 2018 Jun 28.

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

Author information

1
Institute of Human Genetics, UMR9002 CNRS and University of Montpellier, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France.
2
Institute of Human Genetics, UMR9002 CNRS and University of Montpellier, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France. Electronic address: bernd.schuttengruber@igh.cnrs.fr.
3
Department of Computer Science, National Chengchi University, 11605 Taipei City, Taiwan.
4
Institute of Human Genetics, UMR9002 CNRS and University of Montpellier, 141 Rue de la Cardonille, 34396 Montpellier Cedex 5, France. Electronic address: giacomo.cavalli@igh.cnrs.fr.

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.

KEYWORDS:

3D genome; Drosophila embryogenesis; Hi-C; TADs; chromatin; chromosome organization; looping interactions; polycomb

PMID:
30008320
DOI:
10.1016/j.molcel.2018.05.032
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center