Damage-responsive elements in <i>Drosophila</i> regeneration

TLDR

Regenerative biology seeks to understand how gene expression changes trigger regeneration, with injury‑induced resetting governed by coordinated genomic regions controlling multiple DNA‑binding proteins. The study uses genome‑wide chromatin assays to identify regulatory elements controlling tissue recovery in Drosophila imaginal discs after induced cell death. Genome‑wide chromatin profiling was employed to map regulatory elements in regenerating imaginal discs. The study uncovered a globally coregulated regeneration program driven by diverse regulatory elements, including novel damage‑specific enhancers that cooperate with pre‑existing enhancers and harbor binding sites for a conserved set of transcription factors essential for regeneration across metazoans.

Abstract

One of the most important questions in regenerative biology is to unveil how and when genes change expression and trigger regeneration programs. The resetting of gene expression patterns during response to injury is governed by coordinated actions of genomic regions that control the activity of multiple sequence-specific DNA binding proteins. Using genome-wide approaches to interrogate chromatin function, we here identify the elements that regulate tissue recovery in Drosophila imaginal discs, which show a high regenerative capacity after genetically induced cell death. Our findings indicate there is global coregulation of gene expression as well as a regeneration program driven by different types of regulatory elements. Novel enhancers acting exclusively within damaged tissue cooperate with enhancers co-opted from other tissues and other developmental stages, as well as with endogenous enhancers that show increased activity after injury. Together, these enhancers host binding sites for regulatory proteins that include a core set of conserved transcription factors that control regeneration across metazoans.