Fine Tuning of Craniofacial Morphology by Distant-Acting in vivo Enhancers
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Alex Nord
PROVIDER: E-GEOD-49413 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
Fine tuning of craniofacial morphology by distant-acting enhancers.
Attanasio Catia C Nord Alex S AS Zhu Yiwen Y Blow Matthew J MJ Li Zirong Z Liberton Denise K DK Morrison Harris H Plajzer-Frick Ingrid I Holt Amy A Hosseini Roya R Phouanenavong Sengthavy S Akiyama Jennifer A JA Shoukry Malak M Afzal Veena V Rubin Edward M EM FitzPatrick David R DR Ren Bing B Hallgrímsson Benedikt B Pennacchio Len A LA Visel Axel A
Science (New York, N.Y.) 20131001 6157
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 r ...[more]
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Project description:The shape of the human face is largely genetically determined, but the genetic drivers of craniofacial morphology remain poorly understood. In particular, little is known about the contributions of gene regulatory sequences active in the developing face to craniofacial morphology. Here we used a combination of epigenomic profiling, in vivo characterization of more than 200 craniofacial 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 with thousands of enhancers genome-wide that drive a remarkable spatial complexity of in vivo expression patterns. The ChIP-seq experiments in this entry was the basis for the genome-wide analysis of craniofacial enhancers and served as the source for substantialin vivo characterization via transgenic reporter mice and for enhancer knockout experiments.
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