Dynamic 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. 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.

• Publication year

  2024

• Venue

  Nature Communications

• Publication date

  2024-03-06

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/s41467-024-46396-4PMID 38448444PMCID 10917818
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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