期刊
MOLECULAR CELL
卷 71, 期 1, 页码 73-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2018.05.032
关键词
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资金
- European Research Council (FlyingPolycomb
- FP7-IDEAS-ERC) [232947]
- CNRS
- FP7 European Network of Excellence EpiGeneSys (FP7-HEALTH) [257082]
- European Union's Horizon 2020 research and innovation programme [676556]
- Agence Nationale de la Recherche [ANR-15-CE12-006-01]
- Fondation pour la Recherche Medicale [DEI20151234396]
- INSERM
- ITMO Cancer (MMTT)
- French National Cancer Institute (INCa) [PLBIO16-222]
- Laboratory of Excellence EpiGenMed (Investissements d'Avenir programme) [ANR-10-LABX-12-01]
- JSPS Overseas Research Fellowships (Japan Society for the Promotion of Science)
- Taiwan Ministry of Science and Technology [MOST 105-2218-E-004-003, MOST 106-2221-E-004-011-MY2]
- European Research Council (ERC) [232947] Funding Source: European Research Council (ERC)
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.
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