Interplay of genome topology and transcriptional regulation at zebrafish Zygotic Genome Activation
Evolutionary Cell and Developmental Biology (Zoology)
Final Report Abstract
The initiation of transcription during development, or zygotic genome activation (ZGA), is accompanied by massive changes in chromosome organization. However, the earliest events of chromosome folding and their functional roles remain unclear. During the reported project, we discovered that chromosome folding begins after ZGA with the formation of "fountains”: patterns of contacts that emanate from active and latent developmental enhancers. In zebrafish, knockouts of pioneer transcription factors driving ZGA result in the specific loss of fountains on their binding sites. Cohesin-dependent fountains also form on enhancers in mouse cell lines. Polymer simulations demonstrate that fountains may arise as sites of facilitated cohesin loading. Overall, we found that early enhancers direct three-dimensional genome organization during development, and fountains represent universal enhancer-specific chromosome folding elements.
Publications
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Extrusion fountains are hallmarks of chromosome organization emerging upon zygotic genome activation. openRxiv.
Galitsyna, Aleksandra; Ulianov, Sergey; Bazarevich, Mariia; Bykov, Nikolai; Veil, Marina; Gao, Meijiang; Perevoshchikova, Kristina Y.; Gelfand, Mikhail S.; Razin, Sergey V.; Mirny, Leonid A. & Onichtchouk, Daria
