Dynamic enhancer landscapes in human craniofacial development

• Published in: Nature communications Vol. 15; no. 1; p. 2030
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06-03-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 14/35; 14/63; 38/22; 38/39; 45/15; 45/22; 45/23; 45/77; 45/91; 631/136/1660; 631/136/2086; 631/208/191; 64; 64/110; 64/60; Accessibility; Birth defects; Chromatin; Congenital defects; Craniofacial growth; Developmental stages; embryogenesis; Enhancers; functional genomics; Gene expression; Gene mapping; Genetic resources; Genetics; Genomes; Histones; Humanities and Social Sciences; Morphogenesis; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-46396-4

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.
Rajderkar et al. provide a genome-wide compendium of transcriptional enhancers active in human craniofacial development, along with single-cell resources for studies of mammalian craniofacial morphogenesis.