CCAAT/enhancer-binding protein delta (C/EBPdelta) maintains amelogenin expression in the absence of C/EBPalpha in vivo.
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.
Xu
Yucheng
Y
The Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California 90033, USA.
Zhou
Yan Larry
YL
Gonzalez
Frank J
FJ
Snead
Malcolm L
ML
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
D053523:Amelogenin; D022763:CCAAT-Enhancer-Binding Protein-alpha; D053547:Keratin-14; D012333:RNA, Messenger; D051743:CCAAT-Enhancer-Binding Protein-delta
Biochem Biophys Res Commun. 2007 Mar 2;354(1):56-61
17210130
Eur J Oral Sci. 2006 May;114 Suppl 1:169-77; discussion 201-2, 381
16674681
Nat Genet. 1999 Jan;21(1):70-1
9916792
Evol Dev. 2005 Sep-Oct;7(5):440-57
16174037
Mol Cell Biol. 2000 Oct;20(19):7292-9
10982846
Development. 2001 Mar;128(5):675-88
11171393
J Biol Chem. 2000 Apr 21;275(16):12273-80
10766866
J Biol Chem. 2000 Sep 15;275(37):29066-75
10859305
Development. 2004 Oct;131(20):4907-19
15371307
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12532-7
11606718
Mol Cell Biol. 1997 Oct;17(10):6014-22
9315660
J Biol Chem. 1996 Oct 4;271(40):24753-60
8798745
Science. 1995 Aug 25;269(5227):1108-12
7652557
J Biol Chem. 1996 Feb 16;271(7):3891-6
8632009
Development. 1988 Sep;104(1):77-85
3253061
Blood. 2002 Mar 15;99(6):2032-6
11877276
J Biol Chem. 2006 Jun 9;281(23):16090-8
16595692
J Biol Chem. 2004 Oct 22;279(43):44740-8
15292250
J Biol Chem. 2004 Jul 16;279(29):29902-10
15150264
Dev Dyn. 2004 Sep;231(1):98-108
15305290
Dev Biol. 1984 Jul;104(1):255-8
6734939
Arch Oral Biol. 1996 Nov;41(11):1019-27
9068866