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 Celljournal_title
Molecular cellauthors
Ogiyama Y,Schuettengruber B,Papadopoulos GL,Chang JM,Cavalli Gdoi
10.1016/j.molcel.2018.05.032subject
Has Abstractpub_date
2018-07-05 00:00:00pages
73-88.e5issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(18)30407-6journal_volume
71pub_type
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