1443 Skin regional specificity and the regulation of HoxC gene cluster

Skin exhibits remarkable regional specificity. However, the epigenetic mechanism underlying this process remains elusive. In study, we used avian scalp skin as a model and leveraged finding that tandem 195-bp duplication in intron of HoxC10 causes chicken Crest phenotype. Crested chickens (e.g., Polish chickens) exhibit elongated feathers region comb is minute. Along anterior-posterior midline dermis control White Leghorn chicken, showed co-linear expression HoxC members (using RNA seq,in situ hybridization), which correlated with region-specific chromatin accessibility ATAC seq). Configurations topologically associating domains (TADs) over gene cluster scalp, dorsal tail show reduced interactions outside regulatory elements particularly Micro-C). contrast, crested TAD configuration similar to found dermis. HoxC8 over-expression led new feather bud formation at expense domain, representing homeotic transformation. Further analyses revealed six transcription factors major potential upstream modulators region, tandemly duplicated 195 bp may facilitate generation ectopic loops interact distant putative enhancers. Our results provide clue dissect how regulated different regions, setting up platform study specificity, can so many diverse appendage phenotypes birds well mammals.