Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Oct;92(4):1805–1811. doi: 10.1172/JCI116770

Distinct nuclear proteins competing for an overlapping sequence of cyclic adenosine monophosphate and negative regulatory elements regulate tissue-specific mouse renin gene expression.

M Horiuchi 1, R E Pratt 1, N Nakamura 1, V J Dzau 1
PMCID: PMC288343  PMID: 8408633

Abstract

The mouse renin locus (Ren-1d) exhibits specific patterns of tissue expression. It is expressed in kidney but not submandibular gland (SMG). This locus contains a negative regulatory element (NRE) and a cAMP responsive element (CRE) that share an overlapping sequence. In the kidney, CRE binding proteins (CREB) and NRE binding proteins (NREB) compete for binding to this sequence, with the CREB having a greater affinity. In the SMG, CREB is inactivated by an inhibitory protein, permitting NREB to bind to the sequence, thus inhibiting Ren-1d expression. We hypothesize that the competition between NREB and CREB for this sequence governs tissue-specific expression of mouse renin. We speculate that this may be a general paradigm that determines tissue-specific gene expression.

Full text

PDF
1806

Images in this article

1807Image
on p.1807
1807Image
on p.1807
1807Image
on p.1807
1807Image
on p.1807
1808Image
on p.1808
1808Image
on p.1808
1808Image
on p.1808
1809Image
on p.1809
1809Image
on p.1809
1809Image
on p.1809
1810Image
on p.1810
1810Image
on p.1810
1810Image
on p.1810

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ballard D. W., Walker W. H., Doerre S., Sista P., Molitor J. A., Dixon E. P., Peffer N. J., Hannink M., Greene W. C. The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function. Cell. 1990 Nov 16;63(4):803–814. doi: 10.1016/0092-8674(90)90146-6. [DOI] [PubMed] [Google Scholar]
  2. Baniahmad A., Muller M., Steiner C., Renkawitz R. Activity of two different silencer elements of the chicken lysozyme gene can be compensated by enhancer elements. EMBO J. 1987 Aug;6(8):2297–2303. doi: 10.1002/j.1460-2075.1987.tb02504.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baniahmad A., Steiner C., Köhne A. C., Renkawitz R. Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site. Cell. 1990 May 4;61(3):505–514. doi: 10.1016/0092-8674(90)90532-j. [DOI] [PubMed] [Google Scholar]
  4. Barrett G., Horiuchi M., Paul M., Pratt R. E., Nakamura N., Dzau V. J. Identification of a negative regulatory element involved in tissue-specific expression of mouse renin genes. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):885–889. doi: 10.1073/pnas.89.3.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  6. Burt D. W., Nakamura N., Kelley P., Dzau V. J. Identification of negative and positive regulatory elements in the human renin gene. J Biol Chem. 1989 May 5;264(13):7357–7362. [PubMed] [Google Scholar]
  7. Chiu R., Angel P., Karin M. Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun. Cell. 1989 Dec 22;59(6):979–986. doi: 10.1016/0092-8674(89)90754-x. [DOI] [PubMed] [Google Scholar]
  8. Deutsch P. J., Jameson J. L., Habener J. F. Cyclic AMP responsiveness of human gonadotropin-alpha gene transcription is directed by a repeated 18-base pair enhancer. Alpha-promoter receptivity to the enhancer confers cell-preferential expression. J Biol Chem. 1987 Sep 5;262(25):12169–12174. [PubMed] [Google Scholar]
  9. Dzau V. J., Burt D. W., Pratt R. E. Molecular biology of the renin-angiotensin system. Am J Physiol. 1988 Oct;255(4 Pt 2):F563–F573. doi: 10.1152/ajprenal.1988.255.4.F563. [DOI] [PubMed] [Google Scholar]
  10. Fabian J. R., Field L. J., McGowan R. A., Mullins J. J., Sigmund C. D., Gross K. W. Allele-specific expression of the murine Ren-1 genes. J Biol Chem. 1989 Oct 15;264(29):17589–17594. [PubMed] [Google Scholar]
  11. Field L. J., Gross K. W. Ren-1 and Ren-2 loci are expressed in mouse kidney. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6196–6200. doi: 10.1073/pnas.82.18.6196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hay N., Takimoto M., Bishop J. M. A FOS protein is present in a complex that binds a negative regulator of MYC. Genes Dev. 1989 Mar;3(3):293–303. doi: 10.1101/gad.3.3.293. [DOI] [PubMed] [Google Scholar]
  13. Horiuchi M., Nakamura N., Tang S. S., Barrett G., Dzau V. J. Molecular mechanism of tissue-specific regulation of mouse renin gene expression by cAMP. Identification of an inhibitory protein that binds nuclear transcriptional factor. J Biol Chem. 1991 Aug 25;266(24):16247–16254. [PubMed] [Google Scholar]
  14. Israël A., Le Bail O., Hatat D., Piette J., Kieran M., Logeat F., Wallach D., Fellous M., Kourilsky P. TNF stimulates expression of mouse MHC class I genes by inducing an NF kappa B-like enhancer binding activity which displaces constitutive factors. EMBO J. 1989 Dec 1;8(12):3793–3800. doi: 10.1002/j.1460-2075.1989.tb08556.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lee C. Q., Miller H. A., Schlichter D., Dong J. N., Wicks W. D. Evidence for a cAMP-dependent nuclear factor capable of interacting with a specific region of a eukaryotic gene. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4223–4227. doi: 10.1073/pnas.85.12.4223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mullins J. J., Burt D. W., Windass J. D., McTurk P., George H., Brammar W. J. Molecular cloning of two distinct renin genes from the DBA/2 mouse. EMBO J. 1982;1(11):1461–1466. doi: 10.1002/j.1460-2075.1982.tb01338.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nakabeppu Y., Nathans D. A naturally occurring truncated form of FosB that inhibits Fos/Jun transcriptional activity. Cell. 1991 Feb 22;64(4):751–759. doi: 10.1016/0092-8674(91)90504-r. [DOI] [PubMed] [Google Scholar]
  18. Nakamura N., Burt D. W., Paul M., Dzau V. J. Negative control elements and cAMP responsive sequences in the tissue-specific expression of mouse renin genes. Proc Natl Acad Sci U S A. 1989 Jan;86(1):56–59. doi: 10.1073/pnas.86.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rice D. A., Aitken L. D., Vandenbark G. R., Mouw A. R., Franklin A., Schimmer B. P., Parker K. L. A cAMP-responsive element regulates expression of the mouse steroid 11 beta-hydroxylase gene. J Biol Chem. 1989 Aug 25;264(24):14011–14015. [PubMed] [Google Scholar]
  20. Savagner P., Miyashita T., Yamada Y. Two silencers regulate the tissue-specific expression of the collagen II gene. J Biol Chem. 1990 Apr 25;265(12):6669–6674. [PubMed] [Google Scholar]
  21. Schütte J., Viallet J., Nau M., Segal S., Fedorko J., Minna J. jun-B inhibits and c-fos stimulates the transforming and trans-activating activities of c-jun. Cell. 1989 Dec 22;59(6):987–997. doi: 10.1016/0092-8674(89)90755-1. [DOI] [PubMed] [Google Scholar]
  22. Williams T. M., Moolten D., Burlein J., Romano J., Bhaerman R., Godillot A., Mellon M., Rauscher F. J., 3rd, Kant J. A. Identification of a zinc finger protein that inhibits IL-2 gene expression. Science. 1991 Dec 20;254(5039):1791–1794. doi: 10.1126/science.1840704. [DOI] [PubMed] [Google Scholar]
  23. Winoto A., Baltimore D. Alpha beta lineage-specific expression of the alpha T cell receptor gene by nearby silencers. Cell. 1989 Nov 17;59(4):649–655. doi: 10.1016/0092-8674(89)90010-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES