Identifying the transcriptional targets of the Drosophila transcription factor Ets21c via Targeted DamID

Tissue homeostasis relies on stem cell activity which drives replacement of differentiated cells to maintain tissue integrity and function. The stress-inducible transcription factor Ets21c promotes tissue renewal in the Drosophila adult intestine by controlling intestinal stem cell proliferation and apoptosis of mature enterocytes. To determine how Ets21c fulfills these distinct tasks in the different cell types of the gut, we exploited a genome-wide in vivo Targeted DamID mapping approach to identify its putative direct targets. In young unstressed midguts, Ets21c contacts regulatory loci occupied by as well as devoid of the Polymerase II binding. Follow-up functional genetic studies in intestinal stem cells and enterocytes demonstrate that Ets21c controls cell type-specific sets of target genes that orchestrate cellular behavior via intrinsic and non-autonomous signaling mechanisms. Ets21c thus emerges as a vital determinant of adult health and lifespan.