Modifications in gene regulation can contribute to the evolution of animal morphologies. Cis-regulatory elements (CREs), which regulate gene expression through higher-order chromatin structures, tend to evolve more rapidly than their target genes, but how this relates to transcriptional evolvability is unclear. To investigate this, Aurélie Hintermann, Denis Duboule and colleagues compare the regulatory landscape of the HoxD cluster in mouse and chicken in two distinct developmental contexts: trunk elongation, which is highly conserved, and skin appendage formation, which likely evolved independently in these species. They show that different sets of Hoxd genes are expressed in mouse whiskers and chicken feather primordia. In the trunk, by contrast, Hoxd1 expression patterns are conserved whereas the expression of neighbouring paralogues varies. The authors further show that the chromatin architecture of the chick HOXD region closely resembles that of the mouse. Despite this conserved topology, species-specific regulatory activities exist; the transcription of specific Hoxd genes in skin appendages involves lineage-specific CREs located in different regions, whereas trunk Hoxd1 expression is driven by an evolutionarily conserved CRE. These and other findings provide insights into how large regulatory landscapes both favour and constrain transcriptional evolvability.
