Hoxc13 Polyglycine Repeat Gain-Of-Function Drives Mammalian Integument Evolution By Altering Targeted Genes And Interactions

This study examines the role of the polyglycine (polyG) repeat in the Hoxc13 protein, which is essential for hair development and mammalian integument evolution. Researchers compared the normal Hoxc13-W protein with the polyG-deleted Hoxc13-S protein in cashmere goats, finding that Hoxc13-W identified significantly more DNA-binding peaks (12,679) than Hoxc13-S (3,634). The polyG fragment enhances Hoxc13's binding to genes involved in hair follicle morphogenesis and cycling, particularly in the Wnt signaling pathway. This suggests that the polyG fragment modulates gene regulatory networks, contributing to the evolution of mammalian skin appendages like hair. The study also highlights the polyG fragment's role in protein conformation and interaction with other proteins, such as Cdx1, affecting downstream signaling and gene expression.