Theses Doctoral

Widespread 3D genome reorganization precedes programmed DNA rearrangement in Oxytricha trifallax

Villano, Danylo Julian

3D genome organization recapitulates genome function, typically at the level of transcriptional state or chromatin state. Ciliates like Oxytricha trifallax possess highly specialized germline genomes, which play a role in sexual development but are largely transcriptionally silent. During Oxytricha development, the germline undergoes genome-wide rearrangement, transforming into a structurally distinct, transcriptionally active somatic genome.

This wholesale rearrangement is programmed by transgenerational RNA copies of the somatic genome, which guide the retention of a small portion of the germline. Retained and eliminated sequences must be distinguished from each other and processed separately, but how this dichotomy is effected spatially or by chromatin organization is unknown. The breadth of Oxytricha genome dynamics presents the possibility of a complex relationship between chromatin architecture and genome function. We present new tools for studying the Oxytricha germline and apply them to map the 3D organization of the genome’s vegetative and developmental states using Hi-C.

We find that the vegetative conformation primes the germline for development, while a massive spatial reorganization of the genome during development differentiates between retained and eliminated regions and precedes rearrangement of DNA. Further experiments suggest a role for RNA-DNA interactions and chromatin remodeling in this reorganization. This evidence supports a critical role for 3D architecture in programmed genome rearrangement.

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More About This Work

Academic Units
Biological Sciences
Thesis Advisors
Landweber, Laura F.
Degree
Ph.D., Columbia University
Published Here
October 4, 2023