Fine tuning of craniofacial morphology by distant-acting enhancers

Catia Attanasio, Alexander Nord, Yiwen Zhu, Matthew J. Blow, Zirong Li, Denise K. Liberton, Harris Morrison, Ingrid Plajzer-Frick, Amy Holt, Roya Hosseini, Sengthavy Phouanenavong, Jennifer A. Akiyama, Malak Shoukry, Veena Afzal, Edward M. Rubin, David R. FitzPatrick, Bing Ren, Benedikt Hallgrímsson, Len A. Pennacchio, Axel Visel

Research output: Contribution to journalArticlepeer-review

156 Scopus citations


The shape of the human face and skull is largely genetically determined. However, the genomic basis of craniofacial morphology is incompletely understood and hypothesized to involve protein-coding genes, as well as gene regulatory sequences. We used a combination of epigenomic profiling, in vivo characterization of candidate enhancer sequences in transgenic mice, and targeted deletion experiments to examine the role of distant-acting enhancers in craniofacial development. We identified complex regulatory landscapes consisting of enhancers that drive spatially complex developmental expression patterns. Analysis of mouse lines in which individual craniofacial enhancers had been deleted revealed significant alterations of craniofacial shape, demonstrating the functional importance of enhancers in defining face and skull morphology. These results demonstrate that enhancers are involved in craniofacial development and suggest that enhancer sequence variation contributes to the diversity of human facial morphology.

Original languageEnglish (US)
Article number1241006
Issue number6157
StatePublished - Jan 1 2013
Externally publishedYes

ASJC Scopus subject areas

  • General


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