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 language | English (US) |
|---|---|
| Article number | 1241006 |
| Journal | Science |
| Volume | 342 |
| Issue number | 6157 |
| DOIs | |
| State | Published - Jan 1 2013 |
| Externally published | Yes |
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Cite this
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 journal › Article
}
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
C2 - 24159046
AN - SCOPUS:84886257610
VL - 342
JO - Science
JF - Science
SN - 0036-8075
IS - 6157
M1 - 1241006
ER -