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 journalArticle

118 Citations (Scopus)

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.

Original languageEnglish (US)
Article number1241006
JournalScience
Volume342
Issue number6157
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

Skull
Regulator Genes
Epigenomics
Transgenic Mice
Proteins

ASJC Scopus subject areas

  • General

Cite this

Attanasio, C., Nord, A., Zhu, Y., Blow, M. J., Li, Z., Liberton, D. K., ... Visel, A. (2013). Fine tuning of craniofacial morphology by distant-acting enhancers. Science, 342(6157), [1241006]. https://doi.org/10.1126/science.1241006

Fine tuning of craniofacial morphology by distant-acting enhancers. / Attanasio, Catia; Nord, Alexander; 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.

In: Science, Vol. 342, No. 6157, 1241006, 01.01.2013.

Research output: Contribution to journalArticle

Attanasio, C, Nord, A, Zhu, Y, Blow, MJ, Li, Z, Liberton, DK, Morrison, H, Plajzer-Frick, I, Holt, A, Hosseini, R, Phouanenavong, S, Akiyama, JA, Shoukry, M, Afzal, V, Rubin, EM, FitzPatrick, DR, Ren, B, Hallgrímsson, B, Pennacchio, LA & Visel, A 2013, 'Fine tuning of craniofacial morphology by distant-acting enhancers', Science, vol. 342, no. 6157, 1241006. https://doi.org/10.1126/science.1241006
Attanasio C, Nord A, Zhu Y, Blow MJ, Li Z, Liberton DK et al. Fine tuning of craniofacial morphology by distant-acting enhancers. Science. 2013 Jan 1;342(6157). 1241006. https://doi.org/10.1126/science.1241006
Attanasio, Catia ; Nord, Alexander ; 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. / Fine tuning of craniofacial morphology by distant-acting enhancers. In: Science. 2013 ; Vol. 342, No. 6157.
@article{2ee99eaa3ea54c7c9d31c862ac833cd8,
title = "Fine tuning of craniofacial morphology by distant-acting enhancers",
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.",
author = "Catia Attanasio and Alexander Nord and Yiwen Zhu and Blow, {Matthew J.} and Zirong Li and Liberton, {Denise K.} and Harris Morrison and Ingrid Plajzer-Frick and Amy Holt and Roya Hosseini and Sengthavy Phouanenavong and Akiyama, {Jennifer A.} and Malak Shoukry and Veena Afzal and Rubin, {Edward M.} and FitzPatrick, {David R.} and Bing Ren and Benedikt Hallgr{\'i}msson and Pennacchio, {Len A.} and Axel Visel",
year = "2013",
month = "1",
day = "1",
doi = "10.1126/science.1241006",
language = "English (US)",
volume = "342",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6157",

}

TY - JOUR

T1 - Fine tuning of craniofacial morphology by distant-acting enhancers

AU - Attanasio, Catia

AU - Nord, Alexander

AU - Zhu, Yiwen

AU - Blow, Matthew J.

AU - Li, Zirong

AU - Liberton, Denise K.

AU - Morrison, Harris

AU - Plajzer-Frick, Ingrid

AU - Holt, Amy

AU - Hosseini, Roya

AU - Phouanenavong, Sengthavy

AU - Akiyama, Jennifer A.

AU - Shoukry, Malak

AU - Afzal, Veena

AU - Rubin, Edward M.

AU - FitzPatrick, David R.

AU - Ren, Bing

AU - Hallgrímsson, Benedikt

AU - Pennacchio, Len A.

AU - Visel, Axel

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84886257610&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84886257610&partnerID=8YFLogxK

U2 - 10.1126/science.1241006

DO - 10.1126/science.1241006

M3 - Article

VL - 342

JO - Science

JF - Science

SN - 0036-8075

IS - 6157

M1 - 1241006

ER -