Sage Journals: Discover world-class research

Abstract

Amelogenin expression is regulated in a cell-type- specific manner. Investigators have previously identified an enhancer element by using the 5′ flanking sequence of the amelogenin promoter. However, the cell-type-specific regulation of the amelogenin gene remains poorly understood. In some genes, the first intron regulates tissue-specific expression. We hypothesized that intron 1 is important for the cell-type-specific regulation of amelogenin expression. We identified a suppressor element between −74 and −464. We also found enhancer activity in intron 1. Additionally, we found that the suppressor element in the promoter region suppressed intron 1 enhancer activity. The suppressor and the enhancers acted in an ameloblast-like cell line, but not in HeLa cells. Mutation of the Oct-1 binding sites reversed the suppressor activity, suggesting that Oct-1 sites are essential for suppression. These results suggest that Oct-1 and intron 1 may contribute to cell-type-specific amelogenin expression.

Get full access to this article

View all access options for this article.

References

Alder H, Yoshinouchi M, Prystowsky MB, Appasamy P, Baserga R (1992). A conserved region in intron 1 negatively regulates the expression of the PCNA gene. Nucleic Acids Res 20:1769–1775.

Bornstein P, McKay J (1988). The first intron of the alpha 1(I) collagen gene contains several transcriptional regulatory elements. J Biol Chem 263:1603–1606.

Bornstein P, McKay J, Liska DJ, Apone S, Devarayalu S (1988). Interactions between the promoter and first intron are involved in transcriptional control of alpha 1(I) collagen gene expression. Mol Cell Biol 8:4851–4857.

Cheng CK, Yeung CM, Hoo RL, Chow BK, Leung PC (2002). Oct-1 is involved in the transcriptional repression of the gonadotropin-releasing hormone receptor gene. Endocrinology 143:4693–4701.

Dignam JD, Lebovitz RM, Roeder RG (1983). Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res 11:1475–1489.

Inman CK, Li N, Shore P (2005). Oct-1 counteracts autoinhibition of Runx2 DNA binding to form a novel Runx2/Oct-1 complex on the promoter of the mammary gland-specific gene beta-casein. Mol Cell Biol 25:3182–3193.

Kawano S, Morotomi T, Toyono T, Nakamura N, Uchida T, Ohishi M, et al. (2002). Establishment of dental epithelial cell line (HAT-7) and the cell differentiation dependent on Notch signaling pathway. Connect Tissue Res 43:409–412.

Kim MK, Lesoon-Wood LA, Weintraub BD, Chung JH (1996). A soluble transcription factor, Oct-1, is also found in the insoluble nuclear matrix and possesses silencing activity in its alanine-rich domain. Mol Cell Biol 16:4366–4377.

Lee L, Stollar E, Chang J, Grossmann JG, O’Brien R, Ladbury J, et al. (2001). Expression of the Oct-1 transcription factor and characterization of its interactions with the Bob1 coactivator. Biochemistry 40:6580–6588.; erratum in Biochemistry 40: 8430, 2001.

10.

Mesplède T, Island ML, Christeff N, Petek F, Doly J, Navarro S (2005). The POU transcription factor Oct-1 represses virus-induced interferon A gene expression. Mol Cell Biol 25:8717–8731.

11.

Rippe RA, Lorenzen SI, Brenner DA, Breindl M (1989). Regulatory elements in the 5′-flanking region and the first intron contribute to transcriptional control of the mouse alpha 1 type I collagen gene. Mol Cell Biol 9:2224–2227.

12.

Ström AC, Forsberg M, Lillhager P, Westin G (1996). The transcription factors Sp1 and Oct-1 interact physically to regulate human U2 snRNA gene expression. Nucleic Acids Res 24:1981–1986.

13.

Thevenin C, Lucas BP, Kozlow EJ, Kehri JH (1993). Cell type- and stage-specific expression of the CD201B1 antigen correlates with the activity of a diverged octamer DNA motif present in its promoter. J Biol Chem 268:5945–5946.

14.

Weiser MC, Grieshaber NA, Schwartz PE, Majack RA (1997). Perlecan regulates Oct-1 gene expression in vascular smooth muscle cells. Mol Biol Cell 8:999–1011.

15.

Xu L, Harada H, Yokohama-Tamaki T, Matsumoto S, Tanaka J, Taniguchi A (2006a). Reuptake of extracellular amelogenin by dental epithelial cells results in increased levels of amelogenin mRNA through enhanced mRNA stabilization. J Biol Chem 281:2257–2262.

16.

Xu L, Harada H, Taniguchi A (2006b). The exon 6ABC region of amelogenin mRNA contribute to increased levels of amelogenin mRNA through amelogenin protein-enhanced mRNA stabilization. J Biol Chem 281:32439–32444.

17.

Xu L, Harada H, Taniguchi A (2008). The effects of LAMP1 and LAMP3 on M180 amelogenin uptake, localization and amelogenin mRNA induction by amelogenin protein. J Biochem 144:531–537.

18.

Xu Y, Zhou YL, Luo W, Zhu QS, Levy D, MacDougald OA, et al. (2006). NF-Y and CCAAT/enhancer-binding protein alpha synergistically activate the mouse amelogenin gene. J Biol Chem 281:16090–16098.

19.

Zhou L, Nian M, Gu J, Irwin DM (2006). Intron 1 sequences are required for pancreatic expression of the human proglucagon gene. Am J Physiol Regul Integr Comp Physiol 290:R634–R641.

20.

Zhou YL, Snead ML (2000). Identification of CCAAT/enhancer-binding protein alpha as a transactivator of the mouse amelogenin gene. J Biol Chem 275:12273–12280.

21.

Zhou YL, Lei Y, Snead ML (2000). Functional antagonism between Msx2 and CCAAT/enhancer-binding protein alpha in regulating the mouse amelogenin gene expression is mediated by protein-protein interaction. J Biol Chem 275:29066–29075.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.60 MB

Identification of a Suppressor Element in the Amelogenin Promoter

Abstract

Get full access to this article

References

Supplementary Material