1. A novel role for condensin in Drosophila neurons
- Author
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Hassan, Amira, Southall, Tony, and Song, Jie
- Subjects
595.77 - Abstract
Condensins are multi-protein complexes that have key functions such as chromosome compaction, regulation of gene expression and 3D chromatin conformations. Despite the wealth of knowledge on condensins in dividing cells, their role in post-mitotic, specialised cells remains largely unknown. In this thesis I explore a novel role for condensin I subunit Cap-G in Drosophila neurons. In vivo evidence suggests that condensin I subunits Cap-G and Barren are expressed and localised in neurons. The generation of an exclusively post-mitotic, neuron-specific knockdown of Cap-G revealed an exciting role for condensin in maintaining neuronal identity and health. Removal of Cap-G from post-mitotic neurons resulted in severe developmental arrest, behavioural defects and an overall disruption of gene expression. Furthermore, knockdown animals exhibited a downregulation of neuron-specific genes and an upregulation of ectopic, non-neuron specific genes, suggesting loss of neuronal identity. Cap-G DNA binding profiles in neuronal stem cells and neurons reveal dynamic, cell-specific binding of Cap-G across cell types. Moreover, genes bound by Cap-G significantly overlap with the disrupted genes detected in knockdown animals. Overall, the evidence suggests that Cap-G is necessary for healthy neuronal development and maturation and has a neuron-specific, gene regulatory role in Drosophila. The work in this thesis provides the first evidence that condensin is necessary in post-mitotic neurons for transcriptome stability and maintenance of neuronal identity.
- Published
- 2020