Deciphering the Determinants of Genome-Wide Binding of the BET Family Protein BRD4
The Bromodomain and Extraterminal domain (BET) protein family is constituted by: BRDT, BRD2, BRD3, and BRD4. These proteins are characterised by a common structure consisting of two bromodomains and an extraterminal domain. The most widely studied BET protein is BRD4, which has emerged as a key transcription regulator. BRD4 plays a fundamental role in regulating transcription initiation, elongation, and termination. Additionally, BRD4 is enriched in super-enhancers, and although it has been linked to promoter-enhancer contacts, much remains unknown about the underlying mechanism.
The thesis project aims to characterise the main determinants of BRD4 chromatin binding through an integrative computational approach. For this purpose, the project will look for the transcription factors and histone modifications that colocalise with BRD4. Specifically, machine learning algorithms will be used to predict the genomic binding of BRD4.