biostudies-literatureRajderkar SSNIDCR NIH HHSSwiss National Science FoundationNHGRI NIH HHSWellcome TrustU.S. Department of Health & Human Services | National Institutes of Health2030https://www.ebi.ac.uk/biostudies/studies/S-EPMC10917818biostudies-literatureUnknown15(1)The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.Nature communicationsDynamic enhancer landscapes in human craniofacial development.PMC10917818194334R01DE028599U01DE024427186993R01 DE028599U01 DE024427R01 HG003988Visel ANovak CSWang ADickel DEZhu YCook LEKelman GPennacchio LAPreissl SOsterwalder MPlajzer-Frick IParaiso KSpurrell CHWu HBlow MJDarbellay FKato Mvon Maydell KAfzal SYAmaral MLLisgo SAkiyama JAAfzal VBarozzi IRajderkar SSRen BTran SKosicki MHunter RDFukuda-Yuzawa YLin LfalseDynamic enhancer landscapes in human craniofacial development.The genetic basis of human facial variation and craniofacial birth defects remains poorly understood. Distant-acting transcriptional enhancers control the fine-tuned spatiotemporal expression of genes during critical stages of craniofacial development. However, a lack of accurate maps of the genomic locations and cell type-resolved activities of craniofacial enhancers prevents their systematic exploration in human genetics studies. Here, we combine histone modification, chromatin accessibility, and gene expression profiling of human craniofacial development with single-cell analyses of the developing mouse face to define the regulatory landscape of facial development at tissue- and single cell-resolution. We provide temporal activity profiles for 14,000 human developmental craniofacial enhancers. We find that 56% of human craniofacial enhancers share chromatin accessibility in the mouse and we provide cell population- and embryonic stage-resolved predictions of their in vivo activity. Taken together, our data provide an expansive resource for genetic and developmental studies of human craniofacial development.2024-01-01T00:00:00Z2024 Mar2025-04-26T08:06:20.274Z2025-04-06T12:33:35.244ZS-EPMC109178183844844410.1038/s41467-024-46396-4