Journal article
MCS9.7 enhancer activity is highly, but not completely, associated with expression of Irf6 and p63
Developmental Dynamics, Vol.241(2), pp.340-349
02/01/2012
DOI: 10.1002/dvdy.22786
PMCID: PMC4936416
PMID: 22113860
Abstract
BACKGROUND:
DNA variation in Interferon Regulatory Factor 6 (IRF6) contributes risk for orofacial clefting, including a common DNA variant rs642961. This DNA variant is located in a multi-species conserved sequence that is 9.7 kb upstream from the IRF6 transcriptional start site (MCS9.7). The MCS9.7 element was shown to possess enhancer activity that mimicked the expression of endogenous Irf6 at embryonic day 11.5 in transient transgenic embryos, and also contains a p63 binding site that transactivates IRF6 expression. To analyze whether the MCS9.7 enhancer is sufficient to drive IRF6 expression, we generated stable transgenic murine lines that carry a MCS9.7-lacZ transgene. We hypothesized that MCS9.7 was sufficient to recapitulate the endogenous expression of Irf6 at other time-points during embryonic development.
RESULTS:
We observed that MCS9.7 activity recapitulated endogenous Irf6 expression in most tissues, but not in the medial edge epithelium (MEE) at E14.5, when Irf6 expression was high during secondary palatal fusion. Also, while MCS9.7 activity and Irf6 expression were associated with p63 expression, we observed MCS9.7 activity and Irf6 expression in periderm, although p63 was absent.
CONCLUSION:
These data suggest that MCS9.7 enhancer activity is not sufficient to recapitulate IRF6 expression, and that p63 expression is not always necessary nor sufficient for transactivation of IRF6.
Details
- Title: Subtitle
- MCS9.7 enhancer activity is highly, but not completely, associated with expression of Irf6 and p63
- Creators
- Walid D. FakhouriLindsey RheaTianli DuEileen SweezerHarris MorrisonDavid FitzpatrickBaoli Yang - University of IowaMartine DunnwaldBrian C. Schutte
- Resource Type
- Journal article
- Publication Details
- Developmental Dynamics, Vol.241(2), pp.340-349
- DOI
- 10.1002/dvdy.22786
- PMID
- 22113860
- PMCID
- PMC4936416
- NLM abbreviation
- Dev Dyn
- ISSN
- 1058-8388
- Grant note
- Grant support R01 DE013513/DE/NIDCR NIH HHS/United States Medical Research Council/United Kingdom
- Language
- English
- Date published
- 02/01/2012
- Academic Unit
- Craniofacial Anomalies Research Center; Obstetrics and Gynecology
- Record Identifier
- 9983557561202771
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