Fine Tuning of Craniofacial Morphology by Distant-acting Enhancers

Overview

Journal Science

Specialty Science

Date 2013 Oct 26

PMID 24159046

Citations 132

Authors

Catia Attanasio

Alex S 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 Hallgrimsson

Len A Pennacchio

Axel Visel

Affiliations

Soon will be listed here.

Abstract

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.

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