Understanding how uniquely human genetic changes altered developmental processes is essential to understanding human evolution. We investigated the role of the Human Accelerated Region HACNS1 in human limb evolution by directly interrogating its biological functions in a humanized mouse model. Using genome-wide epigenetic profiling, we found that HACNS1 maintains its human-specific transcriptional enhancer activity compared to its chimpanzee ortholog in the mouse embryonic limb, and that it alters promoter activity of the transcription factor gene Gbx2. Using single-cell transcriptional profiling, we demonstrate that Gbx2 is upregulated in humanized limb bud chondrogenic mesenchyme, providing insight into the developmental processes altered due to human-specific alterations in enhancer activity. Our findings establish that HACNS1 directs changes in the level and distribution of gene expression during development, and illustrate how humanized mouse models provide insight into regulatory pathways altered in human evolution. SOURCE: James,P.,Noonan (james.noonan@yale.edu) - Noonan Yale University

Pluto Bioinformatics

GSE141471: The Human Accelerated Region HACNS1 modifies developmental gene expression in humanized mice