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MODULATION OF C/EBPα IN THE REGULATION OF MOUSE
AMELOGENIN TRANSCRIPTION DURING
TOOTH FORMATION
by
Yucheng Xu
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(CRANIOFACIAL BIOLOGY)
December 2006
Copyright 2006 Yucheng Xu
Object Description
| Title | Modulation of C/EBP alpha in the regulation of mouse amelogenin transcription during tooth formation |
| Author | Xu, Yucheng |
| Author email | yuchengx@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Cranio-Facial Biology |
| School | School of Dentistry |
| Date defended/completed | 2006-08-04 |
| Date submitted | 2006 |
| Restricted until | Unrestricted |
| Date published | 2006-10-05 |
| Advisor (committee chair) | Snead, Malcolm L. |
| Advisor (committee member) |
Shuler, Charles Paine, Michael Ann, David K. Sucov, Henry |
| Abstract | Amelogenin gene expression is spatiotemporally regulated during enamel biomineralization. Studies show that C/EBP alpha is a transactivator of the mouse amelogenin gene acting at the C/EBP alpha cis-element located in the -70/+52 minimal promoter that also contains a reversed CCAAT box (-58/-54). Similar to the C/EBP alpha binding site, this CCAAT box is required for the basal promoter activity. Electrophoretic mobility shift assays demonstrate that NF-Y is directly bound to this reversed CCAAT box. Co-transfection of C/EBP alpha and NF-Y synergistically increases the promoter activity. Protein-protein interactions between C/EBP alpha with NF-Y are identified by a co-immunoprecipitation analysis.; A protein/DNA array technique is utilized to identify a transcriptional factor named YY1. YY1 represses both the basal amelogenin promoter activity and C/EBP alpha-mediated transactivation. Furthermore, YY1 repression is independent of its DNA binding capacity.; C/EBP alpha contains four highly conserved regions (CR) named CR1, CR2, CR3 and CR4. CR2 in isolation has an exceptional capacity to activate the full-length amelogenin promoter, while the remaining conserved region, either in isolation or in selected combinations, is less effective. Msx2 has previously been shown to antagonize C/EBP alpha through protein-protein interactions with C/EBP alpha. Co-immunoprecipitation analyses identify that the C-terminal domain (residues 216-359) of C/EBP alpha is required for protein-protein interactions with Msx2.; In LS8 cells, C/EBP alpha is subject to one of the post-translational modification named sumoylation. Sumoylation decreases C/EBP alpha-mediated amelogenin promoter transactivation. In addition, sumoylation of C/EBP alpha is not involved in regulating C/EBP alpha cytoplasmic-nuclear transport.; The neonatal lethal phenotype of C/EBP alpha-deficient mice prevents observing the effects of loss-of-C/EBP alpha on postnatal tooth formation. The Cre/loxP recombination system is utilized to generate the conditional knock-out mice by mating mice bearing the floxed C/EBP alpha alleles with hK14-Cre mice. Real-time PCR analysis shows that removal of one C/EBP alpha allele results in a dramatic decrease of endogenous C/EBP alpha levels and a coordinated marginal decrease in amelogenin levels. However, deletion of both C/EBP alpha alleles fails to ablate amelogenin levels, suggesting an alternative pathway to compensate the loss-of-C/EBP alpha. The fact thatC/EBP delta is able to activate the mouse amelogenin promoter and localizes in the ameloblast cell lineage suggests a functional redundancy between C/EBP delta and C/EBP alpha to produce enough amelogenin proteins. |
| Keyword | amelogenin; gene regulation; C/EBP alpha |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m83 |
| Rights | Xu, Yucheng |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Xu-20061005 |
| Archival file | uscthesesreloadpub_Volume23/etd-Xu-20061005.pdf |
Description
| Title | Page 1 |
| Full text | MODULATION OF C/EBPα IN THE REGULATION OF MOUSE AMELOGENIN TRANSCRIPTION DURING TOOTH FORMATION by Yucheng Xu A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (CRANIOFACIAL BIOLOGY) December 2006 Copyright 2006 Yucheng Xu |
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