Characterising the function and evolution of enhancers in Drosophila

Enhancers are important modular cis-regulatory elements that precisely control the spatial and temporal expression of most genes. Therefore understanding how enhancers work and evolve is crucial for understanding the regulation of most developmental processes in animals. In my PhD project, I investigated three important aspects of enhancers to further our understanding of these cis-regulatory elements: enhancer identification, enhancer functionality and enhancer evolution. I identified a novel post-embryonic enhancer of the Hox gene Ubx, which provides new insights into how Hox genes are integrated into post-embryonic GRNs that determine fine-scale adult morphology. To help understand the cis-regulatory logic of enhancers, I focussed on a functionally related set of genes in a well characterised gene regulatory network. I identified a common pattern of motifs in candidate enhancers, which evidences that this approach may be a powerful for identifying key transcription factor binding sites in enhancers and de novo enhancer prediction. Finally, I described the evolutionary turnover of binding sites and intervening sequences among natural variants of the Drosophila hb P2 enhancer. This suggests that by studying the mutations gained through evolution we can learn more about flexibility and constraints in enhancers and improve on our current knowledge. I then generated tools for the detailed functional comparison of these natural variants, and observed qualitative differences in their function between species. These tools can now be applied to quantify these differences and shows this approach has great potential to better understand the function and evolution other developmental enhancers. Taken together my investigation has broadly contributed to our knowledge of enhancer organisation and functionality and provides a very useful platform for future analyses.

Grantor dc:publisher

Oxford Brookes University

Year dc:date

2019

Author dc:creator

• Buffry, Alexandra D.

Statement dc:rights

• All rights reserved

Language dc:language

en

DOI dc:identifier

https://doi.org/10.24384/re1v-5k80

OAI identifier oai:identifier

tle:237e4501-781f-4905-ae55-4b829de889c7:d6bd9758-527a-46cd-bfe2-c433766e8fca:1