Abstract
dc:description.abstractTransposable elements (TEs) and repetitive sequences make up a significant portion of eukaryotic genomes and their uncontrolled activity can lead to genomic instability. In Drosophila ovaries, silencing of these elements is tightly regulated through the establishment of heterochromatin which prevents TE mobilisation. Piwi guided by piRNAs to nascent TE transcripts, it recruits factors necessary for creating transcriptionally repressive chromatin. Maelstrom, a protein that is involved in transposon silencing within the Drosophila germline, appears to function in both transcriptional (TGS) and post-transcriptional gene silencing (PTGS) pathways. The role of Maelstrom in TGS is investigated in the first chapter and specifically its involvement in the Piwi-dependent silencing machinery that represses transposons by modifying chromatin. Maelstrom plays an important role in this process by regulating the SUMOylation of Panoramix (Panx), which is a core component of the Panoramix-induced co-transcriptional silencing (PICTS) complex. The absence of Maelstrom leads to a reduction in Panx SUMOylation, compromising Panx’s ability to recruit chromatin-modifying proteins and silence transposons effectively. Maelstrom is a putative regulatory factor positioned downstream of Piwi and Arx and upstream of Panx, linking the target recognition with heterochromatin establishment. Outside the nucleus, Maelstrom’s role in PTGS within the nuage of Drosophila germline cells was then investigated in the second chapter. Maelstrom is not directly involved in piRNA biogenesis, and it plays a role in regulating transposon silencing via H3K9me3 modification at transposon loci in the germline. The study demonstrates that Maelstrom interacts with other nuage components, including Spindle-E (Spn-E), Squash (Squ) and Tejas (Tej), possibly forming a complex that functions in PTGS. The interaction between Maelstrom and Tejas, mediated by Maelstrom’s C-terminal domain is essential for linking Maelstrom with Spn-E and Squ. Interestingly, despite the high conservation levels of Mael, certain interactions, such as with Tejas, may be absent in other species like the silkworm, indicating functional divergence across species. This research has expanded our understanding of how small RNAs influence chromatin organisation for transposon silencing.
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
-
- Frantzis, Vasileios
- Advisor dc:contributor.advisor
-
- Hannon, Gregory
Subjects
dc:subject × 8Rights
dc:rightsIdentifiers
dc:identifier.*- DOI dc:identifier.doi
- https://doi.org/10.17863/CAM.118049
- OAI identifier oai:identifier
- oai:www.repository.cam.ac.uk:1810/383817