University of Cambridge
Transcriptional regulation of the piRNA pathway in animal ovarian germ cells
Abstract
dc:description.abstractThe PIWI-interacting RNA (piRNA) pathway is a deeply conserved mechanism by which animals guard their genomes against the activity of mobile genetic elements. The gene-regulatory networks controlling the expression of the germline piRNA pathway components within the gonads of metazoan species remain largely unexplored. In contrast to the male germline piRNA pathway, which in mice is known to be activated by the testis-specific transcription factor A-MYB, the nature of the ovary-specific gene-regulatory network driving the female germline piRNA pathway remains a mystery. In the first chapter, using Drosophila as a model, I combine multiple genomics approaches and reveal the transcription factor Ovo as the master regulator of the germline piRNA pathway in Drosophila ovaries. The enforced expression of Ovo in somatic cells activates expression of germline piRNA pathway components, including the ping-pong factors Aubergine, Argonaute-3 and Vasa, leading to assembly of peri-nuclear cellular structures resembling nuage bodies of animal germ cells. In the second chapter, I extend my analysis to other metazoan species by performing cross-species ATAC-seq, ChIP-seq, RNA-seq and motif analyses and demonstrate that Ovo homologs (e.g., OVOL2 in human) similarly bind to genomic CCGTTA motifs within the promoters of germline piRNA pathway components in mice and human, suggesting a regulation by Ovo in ovaries analogous to that of A-MYB in testes. The results show consistent engagement of the Ovo transcription factor family at ovarian piRNA clusters across metazoan species, reflecting a deep evolutionary conservation of this regulatory paradigm from flies to humans. In the third chapter, I decipher the transcriptional regulation of the soma-expressed piRNA pathway components by the transcription factor Tj in Drosophila ovary somatic follicle cells which suppresses gypsy transposon mobilization from soma to germline. Overall, the results of my thesis reveal the conserved transcription factor Ovo as the master regulator of the female germline piRNA pathway in Drosophila ovaries and provide evidence that this function is broadly conserved amongst animals while the somatic piRNA pathway is controlled by the somatic-enriched transcription factor Tj in Drosophila ovary follicle cells preventing transposon mobilization and invasion into germline.
Degree
thesis:*- Name dc:type.qualificationname
- Doctor of Philosophy (PhD)
- Level dc:type.qualificationlevel
- Doctoral
- Grantor dc:publisher.institution
- University of Cambridge
- Year dc:date.issued
- 2024
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Alizada, Azad
- Advisors dc:contributor.advisor
-
- Nicholson, Benjamin
- Hannon, Gregory
Subjects
dc:subject × 10Rights
dc:rightsIdentifiers
dc:identifier.*- Author Identifier
- 0000-0002-2313-965X
- OAI identifier oai:identifier
- oai:www.repository.cam.ac.uk:1810/383863