The evolutionary origin of DNA accessibility of a new cis-regulatory activity

• Applicant: Professor Dr. Nicolas Gompel
• Subject Area: General Genetics and Functional Genome Biology ; Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409129661

The evolution of animal forms is driven to a large extent by changes in the expression of developmental genes into new expression patterns. These changes are often governed by regulatory changes, such as the gain of new cis-regulatory elements (CREs) or the modification of existing CREs controlling the transcription of a gene. These DNA sequences, modulating at a distance the places, times and levels at which particular genes are transcribed, accomodate the binding of transcription factors (TFs) controlling their activity. To be active, however, CREs also need to be accessible, i.e. no covered by nucleosomes, unlike the majority of the genome sequence. The emergence of a new CRE therefore takes 2 steps, the acquisition of TF binding sites, and the gain of accessibility to its sequence.This proposal examines the relationship between these 2 steps during the evolutionary emergence of a new CRE. We focus on a defined evolutionary transition, the gain of a spot of dark pigment at the tip of the wings in some Drosophila species, that involves the emergence of a new CRE of the pigmentation gene yellow, the spot CRE. Using different species from this group of flies that represent either the ancestral unspotted state, or the derived spotted state, we will examine the activity and accessibility of the region containing this element. In particular, we will disentangle the origin of DNA accessibility from the information imparting the spatial activity of the CRE.In a first project, we will describe the evolutionary and developmental origin of the spot CRE accessibility using ATAC-seq on Drosophila pupal wings. We will further map the determinants regulating this accessibility, and test the possible direct control by the chromatin factor trithorax, that we identified in a previous genetic screen.In a second, independent project, we will determine the functional boundaries of the spot CRE to ask how they relate to the accessibility of the region. Although DNA accessibility combined to chromatin marks is often used as a proxy for enhancer boundaries, there is no quantitative data on the actual relationship between both. We will use a custom quantitative imaging system to precisely map spatial CRE activity in the wings. This mapping will reveal the exact segment of DNA under natural selection and thereby representing the full spot CRE evolutionary unit.Altogether, this proposal will shed light on the relationship between CRE activity and accessibility, and importantly on the evolutionary origin of this accessibility, a key step in the emergence of a new regulatory activity.

• DFG Programme: Research Grants