title: CCAAT/enhancer-binding protein delta (C/EBPdelta) maintains amelogenin expression in the absence of C/EBPalpha in vivo.
abstract: C/EBPalpha is implicated to regulate mouse amelogenin gene expression during tooth enamel formation in vitro. Because enamel formation occurs during postnatal development and C/EBPalpha-deficient mice die at birth, we used the Cre/loxP recombination system to characterize amelogenin expression in C/EBPalpha conditional knock-out mice. Mice carrying the Cre transgene under the control of the human keratin-14 promoter show robust Cre expression in the ameloblast cell lineage. Mating between mice bearing the floxed C/EBPalpha allele with keratin-14-Cre mice generate C/EBPalpha conditional knock-out mice. Real-time PCR analysis shows that removal of one C/EBPalpha allele from the molar enamel epithelial organ of 3-day postnatal mice results in dramatic decrease in endogenous C/EBPalpha mRNA levels and coordinately altered amelogenin mRNA abundance. Conditional deletion of both C/EBPalpha alleles further diminishes C/EBPalpha mRNA levels; however, rather than ablating amelogenin expression, we observe wild-type amelogenin mRNA abundance levels. We examined C/EBPbeta and nuclear factor YA expression, two transcription factors that had previously been shown to modestly participate in amelogenin expression, in vitro but found no significant changes in either of their mRNA abundance levels comparing conditional knock-out mice with wild-type counterparts. Although the abundance of C/EBPdelta is also unchanged in C/EBPalpha conditional knock-out mice, in vitro we find that C/EBPdelta activates the mouse amelogenin promoter and synergistically cooperates with nuclear factor Y, suggesting that C/EBPdelta can functionally substitute for C/EBPalpha to produce an enamel matrix competent to direct biomineralization.
authors: The Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA.
authors: Yucheng
authors: Y
authors: Xu
authors: Yan Larry
authors: YL
authors: Zhou
authors: Frank J
authors: FJ
authors: Gonzalez
authors: Malcolm L
authors: ML
authors: Snead
mesh_terms: D000483:Alleles; D053523:Amelogenin / Q000096:biosynthesis*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism / Q000502:physiology*; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000378:metabolism / Q000502:physiology*; D019070:Cell Lineage; D003743:Dental Enamel / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D053547:Keratin-14 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D053523:Amelogenin; D022763:CCAAT-Enhancer-Binding Protein-alpha; D053547:Keratin-14; D012333:RNA, Messenger; D051743:CCAAT-Enhancer-Binding Protein-delta
references: Biochem Biophys Res Commun. 2007 Mar 2;354(1):56-61
references: 17210130
references: Eur J Oral Sci. 2006 May;114 Suppl 1:169-77; discussion 201-2, 381
references: 16674681
references: Nat Genet. 1999 Jan;21(1):70-1
references: 9916792
references: Evol Dev. 2005 Sep-Oct;7(5):440-57
references: 16174037
references: Mol Cell Biol. 2000 Oct;20(19):7292-9
references: 10982846
references: Development. 2001 Mar;128(5):675-88
references: 11171393
references: J Biol Chem. 2000 Apr 21;275(16):12273-80
references: 10766866
references: J Biol Chem. 2000 Sep 15;275(37):29066-75
references: 10859305
references: Development. 2004 Oct;131(20):4907-19
references: 15371307
references: Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12532-7
references: 11606718
references: Mol Cell Biol. 1997 Oct;17(10):6014-22
references: 9315660
references: J Biol Chem. 1996 Oct 4;271(40):24753-60
references: 8798745
references: Science. 1995 Aug 25;269(5227):1108-12
references: 7652557
references: J Biol Chem. 1996 Feb 16;271(7):3891-6
references: 8632009
references: Development. 1988 Sep;104(1):77-85
references: 3253061
references: Blood. 2002 Mar 15;99(6):2032-6
references: 11877276
references: J Biol Chem. 2006 Jun 9;281(23):16090-8
references: 16595692
references: J Biol Chem. 2004 Oct 22;279(43):44740-8
references: 15292250
references: J Biol Chem. 2004 Jul 16;279(29):29902-10
references: 15150264
references: Dev Dyn. 2004 Sep;231(1):98-108
references: 15305290
references: Dev Biol. 1984 Jul;104(1):255-8
references: 6734939
references: Arch Oral Biol. 1996 Nov;41(11):1019-27
references: 9068866