Identification of Novel Craniofacial Regulatory Domains Located far Upstream of SOX9 and Disrupted in Pierre Robin Sequence.

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Serval ID
serval:BIB_9CED07B2960E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of Novel Craniofacial Regulatory Domains Located far Upstream of SOX9 and Disrupted in Pierre Robin Sequence.
Journal
Human Mutation
Author(s)
Gordon C.T., Attanasio C., Bhatia S., Benko S., Ansari M., Tan T.Y., Munnich A., Pennacchio L.A., Abadie V., Temple I.K., Goldenberg A., van Heyningen V., Amiel J., FitzPatrick D., Kleinjan D.A., Visel A., Lyonnet S.
ISSN
1098-1004 (Electronic)
ISSN-L
1059-7794
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
35
Number
8
Pages
1011-1020
Language
english
Abstract
Mutations in the coding sequence of SOX9 cause campomelic dysplasia (CD), a disorder of skeletal development associated with 46,XY disorders of sex development (DSDs). Translocations, deletions, and duplications within a ∼2 Mb region upstream of SOX9 can recapitulate the CD-DSD phenotype fully or partially, suggesting the existence of an unusually large cis-regulatory control region. Pierre Robin sequence (PRS) is a craniofacial disorder that is frequently an endophenotype of CD and a locus for isolated PRS at ∼1.2-1.5 Mb upstream of SOX9 has been previously reported. The craniofacial regulatory potential within this locus, and within the greater genomic domain surrounding SOX9, remains poorly defined. We report two novel deletions upstream of SOX9 in families with PRS, allowing refinement of the regions harboring candidate craniofacial regulatory elements. In parallel, ChIP-Seq for p300 binding sites in mouse craniofacial tissue led to the identification of several novel craniofacial enhancers at the SOX9 locus, which were validated in transgenic reporter mice and zebrafish. Notably, some of the functionally validated elements fall within the PRS deletions. These studies suggest that multiple noncoding elements contribute to the craniofacial regulation of SOX9 expression, and that their disruption results in PRS.
Keywords
SOX9, craniofacial, enhancer, Pierre Robin, long-range regulation, campomelic dysplasia
Pubmed
Web of science
Create date
21/08/2014 8:45
Last modification date
20/08/2019 15:03
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