Fine tuning of craniofacial morphology by distant-acting enhancers.

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Attanasio, Catia; Nord, Alex S; Zhu, Yiwen; Blow, Matthew J; Li, Zirong; Liberton, Denise K; Morrison, Harris; Plajzer-Frick, Ingrid; Holt, Amy; Hosseini, Roya; Phouanenavong, Sengthavy; Akiyama, Jennifer A; Shoukry, Malak; Afzal, Veena; Rubin, Edward M; FitzPatrick, David R; Ren, Bing; Hallgrímsson, Benedikt; Pennacchio, Len A; Visel, Axel
Year of Publication: 2013
Journal: Science
Volume: 342
Issue: 6157
Pagination: 1241006
Date Published: 2013 Oct 25
Publication Language: eng
ISSN: 1095-9203
Keywords: Animals, Craniofacial Abnormalities, Enhancer Elements, Genetic, Epigenesis, Genetic, Face, Gene Expression Profiling, Gene Expression Regulation, Developmental, Gene Targeting, Maxillofacial Development, Mice, Mice, Transgenic, Sequence Deletion, Skull

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.

DOI: 10.1126/science.1241006
Alternate Journal: Science