- Rajderkar, Sudha Sunil;
- Paraiso, Kitt;
- Amaral, Maria Luisa;
- Kosicki, Michael;
- Cook, Laura E;
- Darbellay, Fabrice;
- Spurrell, Cailyn H;
- Osterwalder, Marco;
- Zhu, Yiwen;
- Wu, Han;
- Afzal, Sarah Yasmeen;
- Blow, Matthew J;
- Kelman, Guy;
- Barozzi, Iros;
- Fukuda-Yuzawa, Yoko;
- Akiyama, Jennifer A;
- Afzal, Veena;
- Tran, Stella;
- Plajzer-Frick, Ingrid;
- Novak, Catherine S;
- Kato, Momoe;
- Hunter, Riana D;
- von Maydell, Kianna;
- Wang, Allen;
- Lin, Lin;
- Preissl, Sebastian;
- Lisgo, Steven;
- Ren, Bing;
- Dickel, Diane E;
- Pennacchio, Len A;
- Visel, Axel
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.