Mechanisms of 3D genome organization by condensin and its interactors

Presenter(s): Yukiko Gaudreault — Biology

Faculty Mentor(s): Osamu Iwasaki

Session: Oral Panel—Bio-Zebrafish and DNA

It is known that eukaryotic genomes are organized in differently sized chromatin domains, including topologically associating domains (TADs) which organize active and inactive chromatin domains and therefore coregulate transcription. This structure is of great interest because when defective, it can lead to developmental abnormalities and human disease. The in situ Hi-C method has been applied to fission yeast cells to show that the protein complex condensin forms ~500kbp chromosomal domains that are required for proper chromosome segregation during mitosis. However, it is still unclear how condensin domains are formed and regulated during the cell cycle. Here we show several potential condensin interactors involved in the regulation of condensin-mediated domains. To do so, we applied the auxin-inducible degron system to 9 condensin interactor genes that were previously found via yeast-two hybrid screening. Performing in situ Hi-C on these conditional knock-out strains showed that Clc1/ clathrin and Sds3/ histone deacetylase promote the formation of condensin domain and that Fyu1/ UTP-glucose-1-phosphate uridylyltransferase and Pfk1/ 6-phosphofructokinase negatively regulate condensin function. We anticipate these results to drive further investigation into the involvement of metabolic proteins in genome organization, as well as the further understanding of chromosome organization mediated by condensin and its interactors.

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