Gomes Faria, Rosa; (2018) Candidate enhancer and transcription dynamics in early Xenopus tropicalis development. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

A previous study from the Gilchrist lab measured transcription in the Xenopus tropicalis embryo for the first 66 hours of development at a high temporal resolution. This data showed that early transcription in Xenopus tropicalis is a very dynamic process, indicating that the mechanisms regulating it should also present dynamic behaviours. The aim of this project was to understand the dynamics of enhancer usage and investigate whether this correlates with gene transcription, using p300 as an enhancer proxy and Xenopus tropicalis as a model. A 12.5-hour p300 ChIP-seq high-resolution time series, covering the end of the blastula stages, gastrulation and most of neurulation, was generated. ChIP-seq time series data analysis was optimised, including through the development of a normalisation method which allows for varying levels of background reads in different ChIP-seq samples. A dataset of 9,807 candidate enhancers and their respective usage dynamics was generated, a potentially useful tool for the Xenopus community. Furthermore, I showed that p300 binding dynamics at promoters and nearby candidate enhancers correlate well, reinforcing the enhancer-promoter loop model for transcription regulation. Additionally, I showed that p300 binding dynamics at promoters correlate with gene transcription, suggesting that the loop is maintained for the duration of transcription. I used both results to create a method to predict candidate enhancer-gene pairs and, with the addition of differential DNA motif analysis, to predict candidate target genes for some well-known transcription factors. The data generated in this project helped shed light on transcriptional regulation and led to the development of some useful tools both for Xenopus and transcription researchers.

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