Interplay of genome topology and transcriptional regulation at zebrafish Zygotic Genome Activation

• Applicant: Dr. Daria Onichtchouk
• Subject Area: Developmental Biology ; Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 429872256

Recent development of Chromosome Conformation Capture methods, in particular Hi-C, revealed the principles of basic chromatin packaging in the eukaryotic nucleus. Chromatin is organized in 3D structures, topologically associated domains (TADs) and compartments. 3D chromatin organization is dynamically rearranged during early embryo development. In most studied organisms, TADs and compartments gradually emerge with the onset of zygotic transcription (Zygotic Genome Activation, or ZGA). The reasons for this restructuring and the importance of TAD formation for ZGA are unknown. In Drosophila, TAD formation during ZGA partially depends on single ZGA activator Zelda. Several lines of evidence and our pilot experiments suggest that also in zebrafish ZGA activators Pou5f3, SoxB1 and Nanog may be involved in 3D chromatin formation after ZGA. We will test this hypothesis by creating 3D chromatin maps by Hi-C method on the single, double and triple ZGA mutants and comparing them to the wild-type zebrafish embryos before and after ZGA. The results will be analyzed together with chromatin modification maps, accessible chromatin maps and transcriptional changes in the same mutants. The results will deepen our understanding of the mechanisms and functionality of 3D chromatin architecture in development.

• DFG Programme: Research Grants
• International Connection: Russia
• Partner Organisation: Russian Foundation for Basic Research, until 3/2022
• Cooperation Partner: Sergey Ulianov, Ph.D., until 3/2022