Decoding the rules of enhancer - promoter specificity throughout development

Enhancers control spatio-temporal gene expression, which is central to the diversification of cell-types and tissue differentiation.

Enhancers can be located in close proximity to, or distally from, their target genes promoters, including in introns of non-cognate genes.

To regulate gene expression, distal enhancers (E) must come into proximity to interact with their promoters (P) through folding/looping of the intervening DNA.

How enhancers identify and regulate their specific target gene remains poorly understood and is subject of this proposal.

Chromosome conformation capture based techniques such as Nuclear-Titrated (NuTi) Capture-C are powerful tools for the genome-wide investigation of enhancerpromoter proximity/interactions (EPIs) at sub-kilobase resolution.

This project aims to uncover general features of EPIs by measuring and characterizing EPIs using NuTi Capture-C across many different developmental stages and tissues during Drosophila embryogenesis.

I will analyze a massive Capture-C dataset already generated by host lab, capturing interactions from 16,663 genes promoters each at eight different conditions (with four replicates), thereby providing unprecedented scale and resolution.

I will integrate this Capture-C resource with multiple genome-wide datasets (gene expression, histone marks and chromatin accessibility) from the host lab and others.

The analysis of this comprehensive EPIs atlas will link enhancers to promoters (genome-wide), characterize features driving E-P specificity and potentially identify novel factors involved in their establishment.

This new view of tissue- and developmental stage- specific EPIs will serve as a unique resource that we will share through a user-friendly web-based portal to a large community using this important model organism.

The biological insights that we uncover, including features linked to E-P specificity and tissues-specific regulation, will interest a very broad community studying genome regulation.