Fine Tuning of Craniofacial Morphology by Distant-Acting Enhancers

被引：182

作者：

Attanasio, Catia ^{[1
]}

Nord, Alex S. ^{[1
]}

Zhu, Yiwen ^{[1
]}

Blow, Matthew J. ^{[2
]}

Li, Zirong ^{[3
,4
]}

Liberton, Denise K. ^{[5
]}

Morrison, Harris ^{[6
]}

Plajzer-Frick, Ingrid ^{[1
]}

Holt, Amy ^{[1
]}

Hosseini, Roya ^{[1
]}

Phouanenavong, Sengthavy ^{[1
]}

Akiyama, Jennifer A. ^{[1
]}

Shoukry, Malak ^{[1
]}

Afzal, Veena ^{[1
]}

Rubin, Edward M. ^{[1
,2
]}

FitzPatrick, David R. ^{[6
,7
]}

Ren, Bing ^{[3
,4
]}

Hallgrimsson, Benedikt ^{[5
,8
]}

Pennacchio, Len A. ^{[1
,2
]}

Visel, Axel ^{[1
,2
]}

机构：

[1] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA

[2] US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA

[3] Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[5] Univ Calgary, Dept Cell Biol & Anat, McCaig Bone & Joint Inst, Calgary, AB T2N 4N1, Canada

[6] Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[7] Royal Hosp Sick Children, Edinburgh EH9 1LF, Midlothian, Scotland

[8] Univ Calgary, Alberta Childrens Hosp, Res Inst, Calgary, AB T2N 4N1, Canada

来源：

SCIENCE | 2013年 / 342卷 / 6157期

基金：

加拿大自然科学与工程研究理事会; 英国医学研究理事会; 瑞士国家科学基金会;

关键词：

GENOME-WIDE ASSOCIATION; CLEFT-LIP; GENE-EXPRESSION; SONIC HEDGEHOG; CRANIAL BASE; PALATE; REVEALS; HERITABILITY; MUTATIONS; FAMILY;

D O I：

10.1126/science.1241006

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

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