The Ghavi-Helm Laboratory

Enhancer-promoter interactions

 My recent work suggests that (i) developmental genes are often regulated by multiple enhancers, sometimes located at great linear distances, (ii) the spatio-temporal activity of a large fraction of those enhancers remains unknown, (iii) enhancer-promoter interactions are usually established before the target gene is expressed and are largely stable during embryogenesis, and (iv) stable interactions seem to be associated with the presence of paused RNA Polymerase II at the promoter before gene activation.

Research plans

3D regulatory genomics during Drosophila embryogenesis

 Building upon these results, we propose to advance to the next level in the dissection of enhancer-promoter interaction functionality in the context of Drosophila embryogenesis. Specifically, we will address three important questions:

1) What determines the specificity of promoter-enhancer interactions in a complex genome?

2) Are enhancer-promoter interactions tissue-specific, and what are the drivers of this specificity?

3) Are all enhancer-promoter interactions functional, and how does the activity of an enhancer relate to the expression of the gene it interacts with?

Experimental techniques

The main tools used in the lab are:

4C/Hi-C/Capture-C, RNA-seq, ChIP-seq, ATAC-seq, CRISPR-Cas9 genome editing, FACS sorting, Drosophila genetics and transgenesis, bioinformatics.

Our favorite model organism is the fruit fly Drosophila melanogaster.