Journal article
Interferon regulatory factor 6 promotes differentiation of the periderm by activating expression of Grainyhead-like 3
Journal of investigative dermatology, Vol.133(1), pp.68-77
01/2013
DOI: 10.1038/jid.2012.269
PMCID: PMC3541433
PMID: 22931925
Abstract
IFN regulatory factor 6 (IRF6) is a transcription factor that, in mammals, is required for the differentiation of skin, breast epithelium, and oral epithelium. However, the transcriptional targets that mediate these effects are currently unknown. In zebrafish and frog embryos, Irf6 is necessary for differentiation of the embryonic superficial epithelium, or periderm. Here we use microarrays to identify genes that are expressed in the zebrafish periderm and whose expression is inhibited by a dominant-negative variant of Irf6 (dnIrf6). These methods identify Grainyhead-like 3 (Grhl3), an ancient regulator of the epidermal permeability barrier, as acting downstream of Irf6. In human keratinocytes, IRF6 binds conserved elements near the GRHL3 [corrected] promoter. We show that one of these elements has enhancer activity in human keratinocytes and zebrafish periderm, suggesting that Irf6 directly stimulates Grhl3 expression in these tissues. Simultaneous inhibition of grhl1 and grhl3 disrupts periderm differentiation in zebrafish, and, intriguingly, forced grhl3 expression restores periderm markers in both zebrafish injected with dnIrf6 and frog embryos depleted of Irf6. Finally, in Irf6-deficient mouse embryos, Grhl3 expression in the periderm and oral epithelium is virtually absent. These results indicate that Grhl3 is a key effector of Irf6 in periderm differentiation.
Details
- Title: Subtitle
- Interferon regulatory factor 6 promotes differentiation of the periderm by activating expression of Grainyhead-like 3
- Creators
- Gabriel de la Garza - University of IowaJack Robert SchleiffarthMartine DunnwaldAnuj MankadJason L WeiratherGregory BondeStephen ButcherTamer A MansourYoussef A KousaCindy F FukazawaDouglas W HoustonJ Robert ManakBrian C SchutteDaniel S WagnerRobert A Cornell
- Resource Type
- Journal article
- Publication Details
- Journal of investigative dermatology, Vol.133(1), pp.68-77
- DOI
- 10.1038/jid.2012.269
- PMID
- 22931925
- PMCID
- PMC3541433
- NLM abbreviation
- J Invest Dermatol
- ISSN
- 0022-202X
- eISSN
- 1523-1747
- Publisher
- United States
- Grant note
- GM08399904 / NIGMS NIH HHS T32 GM008629 / NIGMS NIH HHS F31 DE022696 / NIDCR NIH HHS DE21071 / NIDCR NIH HHS 5T32DC000040-17 / NIDCD NIH HHS R01 DE021071 / NIDCR NIH HHS 5R37DE008559-21 / NIDCR NIH HHS DE13513 / NIDCR NIH HHS R01GM77429 / NIGMS NIH HHS R01 DE013513 / NIDCR NIH HHS R01 GM083999 / NIGMS NIH HHS R01 GM077429 / NIGMS NIH HHS GM067841 / NIGMS NIH HHS T32 GM082729 / NIGMS NIH HHS 1F31DE022696-01 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS R01 GM067841 / NIGMS NIH HHS T32 DC000040 / NIDCD NIH HHS
- Language
- English
- Date published
- 01/2013
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Biology; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9983992094302771
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