Transcriptional control of C. elegans male tail tip morphogenesis by DMD-3

Sexual dimorphic morphogenesis is governed by DM-domain transcription factors (TFs) in many animals, but how these transcriptional control links to the morphogenetic mechanisms is insufficiently known. The DM-domain TF DMD-3 in C. elegans is the master regulator of a male-specific development that changes the shape of the tail tip from long and pointed in larvae to short and round in adults. This tail tip morphogenesis (TTM) requires cell-shape changes, cell migration and fusion. To understand how transcriptional regulation by DMD-3 governs TTM, we used male-specific ChIP-seq to identify its direct targets. We found 1,755 DMD-3 bound sites. We identify a DMD-3 associated binding motif and validate its function in TTM. This motif is similar to the binding motif of EOR-1, and we suggest that DMD-3 acts cooperatively with EOR-1 and possibly other TFs. DMD-3 targets 270 genes that play a role in TTM. These genes include other TFs but also effectors and components of morphogenetic mechanisms. By deleting the DMD-3 bound region endogenously and observing changes in reporter expression and tail tip phenotypes, we identify tissue specific enhancers in the cis-regulatory region of fos-1, pan-1, nmy-2 and hmr-1 that play a role in TTM. For fos-1, we propose that a feed-forward loop is responsible for tail-tip specific increase of gene-expression. This study provides insights into the architecture of the genetic regulatory network controlling a morphogenetic process. Article SummaryDM domain transcription factors are often responsible for sexually dimorphic morphogenesis, but how they connect to morphogenetic mechanisms is insufficiently known. Here, we use ChIP-seq to determine the direct targets of DMD-3, which is the master regulator of male-specific tail tip morphogenesis (TTM) in C. elegans. We find that DMD-3 targets 270 TTM genes which include other transcription factors but also effectors and components of morphogenetic mechanisms. This study provides insights into the architecture of the genetic regulatory network controlling a morphogenetic process.