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. 1993 Dec 11;21(24):5767–5774. doi: 10.1093/nar/21.24.5767

Expression and differential regulation of Id1, a dominant negative regulator of basic helix-loop-helix transcription factors, in glomerular mesangial cells.

M S Simonson 1, A Rooney 1, W H Herman 1
PMCID: PMC310547  PMID: 8284227

Abstract

Id is a family of dominant negative helix-loop-helix (HLH) proteins that block cell-specific transcription mediated by basic HLH (bHLH) transcription mediated by basic HLH (bHLH) transcription factors. We have analyzed Id1 expression in mesangial cells as a first step towards understanding the putative role of bHLH transcription factors in cell type-specific gene expression in the kidney. Glomerular mesangial cells expressed an abundant 1.1 kb mRNA transcript for Id1, but in contrast to other cell types Id1 mRNA was expressed in both randomly cycling cells and in serum-deprived, quiescent cultures. When quiescent mesangial cells were treated with serum to re-enter G1, Id1 mRNA levels were rapidly (2-4 h) and transiently down-regulated. Down-regulation of Id1 mRNA following addition of serum to mesangial cells was cell type-specific and contrasted with induction of Id1 by serum in BHK-21 and 3T3 fibroblasts. Down-regulation of Id1 mRNA correlated with mitogenesis and occurred when quiescent cells were treated with growth factors that activate G protein-coupled receptors and receptor protein tyrosine kinases but not with a non-mitogenic cAMP analog. Down-regulation of Id1 by growth factors required de novo protein synthesis, suggesting that a labile protein was involved. Appearance of E-box DNA binding activity in mesangial cell extracts followed down-regulation of Id1 message. Steady state Id1 mRNA levels and E-box DNA binding activity were not tightly correlated, suggesting complex regulation of Id1 activity. mRNA transcripts for E2A gene products were also expressed in mesangial cells, but these cells failed to express mRNAs for MyoA/MyoD-related genes. Collectively, these data demonstrate that Id1 is expressed in renal mesangial cells and suggest that bHLH complexes might be important for transcriptional regulation in the kidney. In addition, the observation that Id1 mRNA is transiently down-regulated by serum in mesangial cells suggests that Id1 gene expression is more complicated than previously appreciated and is tightly regulated in a cell-specific manner.

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Selected References

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

  1. Baichwal V. R., Park A., Tjian R. The cell-type-specific activator region of c-Jun juxtaposes constitutive and negatively regulated domains. Genes Dev. 1992 Aug;6(8):1493–1502. doi: 10.1101/gad.6.8.1493. [DOI] [PubMed] [Google Scholar]
  2. Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. doi: 10.1016/0092-8674(90)90214-y. [DOI] [PubMed] [Google Scholar]
  3. Bengal E., Ransone L., Scharfmann R., Dwarki V. J., Tapscott S. J., Weintraub H., Verma I. M. Functional antagonism between c-Jun and MyoD proteins: a direct physical association. Cell. 1992 Feb 7;68(3):507–519. doi: 10.1016/0092-8674(92)90187-h. [DOI] [PubMed] [Google Scholar]
  4. Biggs J., Murphy E. V., Israel M. A. A human Id-like helix-loop-helix protein expressed during early development. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1512–1516. doi: 10.1073/pnas.89.4.1512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blau H. M. Hierarchies of regulatory genes may specify mammalian development. Cell. 1988 Jun 3;53(5):673–674. doi: 10.1016/0092-8674(88)90082-7. [DOI] [PubMed] [Google Scholar]
  6. Brennan T. J., Edmondson D. G., Li L., Olson E. N. Transforming growth factor beta represses the actions of myogenin through a mechanism independent of DNA binding. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3822–3826. doi: 10.1073/pnas.88.9.3822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Christy B. A., Sanders L. K., Lau L. F., Copeland N. G., Jenkins N. A., Nathans D. An Id-related helix-loop-helix protein encoded by a growth factor-inducible gene. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1815–1819. doi: 10.1073/pnas.88.5.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cordle S. R., Henderson E., Masuoka H., Weil P. A., Stein R. Pancreatic beta-cell-type-specific transcription of the insulin gene is mediated by basic helix-loop-helix DNA-binding proteins. Mol Cell Biol. 1991 Mar;11(3):1734–1738. doi: 10.1128/mcb.11.3.1734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davis R. L., Weintraub H., Lassar A. B. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987 Dec 24;51(6):987–1000. doi: 10.1016/0092-8674(87)90585-x. [DOI] [PubMed] [Google Scholar]
  10. Ellis H. M., Spann D. R., Posakony J. W. extramacrochaetae, a negative regulator of sensory organ development in Drosophila, defines a new class of helix-loop-helix proteins. Cell. 1990 Apr 6;61(1):27–38. doi: 10.1016/0092-8674(90)90212-w. [DOI] [PubMed] [Google Scholar]
  11. Garrell J., Modolell J. The Drosophila extramacrochaetae locus, an antagonist of proneural genes that, like these genes, encodes a helix-loop-helix protein. Cell. 1990 Apr 6;61(1):39–48. doi: 10.1016/0092-8674(90)90213-x. [DOI] [PubMed] [Google Scholar]
  12. Gorski D. H., LePage D. F., Patel C. V., Copeland N. G., Jenkins N. A., Walsh K. Molecular cloning of a diverged homeobox gene that is rapidly down-regulated during the G0/G1 transition in vascular smooth muscle cells. Mol Cell Biol. 1993 Jun;13(6):3722–3733. doi: 10.1128/mcb.13.6.3722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Herskowitz I. A regulatory hierarchy for cell specialization in yeast. Nature. 1989 Dec 14;342(6251):749–757. doi: 10.1038/342749a0. [DOI] [PubMed] [Google Scholar]
  14. Jen Y., Weintraub H., Benezra R. Overexpression of Id protein inhibits the muscle differentiation program: in vivo association of Id with E2A proteins. Genes Dev. 1992 Aug;6(8):1466–1479. doi: 10.1101/gad.6.8.1466. [DOI] [PubMed] [Google Scholar]
  15. Kadesch T. Helix-loop-helix proteins in the regulation of immunoglobulin gene transcription. Immunol Today. 1992 Jan;13(1):31–36. doi: 10.1016/0167-5699(92)90201-h. [DOI] [PubMed] [Google Scholar]
  16. Kawaguchi N., DeLuca H. F., Noda M. Id gene expression and its suppression by 1,25-dihydroxyvitamin D3 in rat osteoblastic osteosarcoma cells. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4569–4572. doi: 10.1073/pnas.89.10.4569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kemp P. R., Grainger D. J., Shanahan C. M., Weissberg P. L., Metcalfe J. C. The Id gene is activated by serum but is not required for de-differentiation in rat vascular smooth muscle cells. Biochem J. 1991 Jul 1;277(Pt 1):285–288. doi: 10.1042/bj2770285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kreidberg J. A., Sariola H., Loring J. M., Maeda M., Pelletier J., Housman D., Jaenisch R. WT-1 is required for early kidney development. Cell. 1993 Aug 27;74(4):679–691. doi: 10.1016/0092-8674(93)90515-r. [DOI] [PubMed] [Google Scholar]
  19. Kreider B. L., Benezra R., Rovera G., Kadesch T. Inhibition of myeloid differentiation by the helix-loop-helix protein Id. Science. 1992 Mar 27;255(5052):1700–1702. doi: 10.1126/science.1372755. [DOI] [PubMed] [Google Scholar]
  20. Latta H. An approach to the structure and function of the glomerular mesangium. J Am Soc Nephrol. 1992 Apr;2(10 Suppl):S65–S73. doi: 10.1681/ASN.V210s65. [DOI] [PubMed] [Google Scholar]
  21. Li L., Chambard J. C., Karin M., Olson E. N. Fos and Jun repress transcriptional activation by myogenin and MyoD: the amino terminus of Jun can mediate repression. Genes Dev. 1992 Apr;6(4):676–689. doi: 10.1101/gad.6.4.676. [DOI] [PubMed] [Google Scholar]
  22. Mendel D. B., Crabtree G. R. HNF-1, a member of a novel class of dimerizing homeodomain proteins. J Biol Chem. 1991 Jan 15;266(2):677–680. [PubMed] [Google Scholar]
  23. Mené P., Simonson M. S., Dunn M. J. Physiology of the mesangial cell. Physiol Rev. 1989 Oct;69(4):1347–1424. doi: 10.1152/physrev.1989.69.4.1347. [DOI] [PubMed] [Google Scholar]
  24. Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
  25. Olson E. N. MyoD family: a paradigm for development? Genes Dev. 1990 Sep;4(9):1454–1461. doi: 10.1101/gad.4.9.1454. [DOI] [PubMed] [Google Scholar]
  26. Pongubala J. M., Atchison M. L. Functional characterization of the developmentally controlled immunoglobulin kappa 3' enhancer: regulation by Id, a repressor of helix-loop-helix transcription factors. Mol Cell Biol. 1991 Feb;11(2):1040–1047. doi: 10.1128/mcb.11.2.1040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Simonson M. S., Dunn M. J. Eicosanoid biochemistry in cultured glomerular mesangial cells. Methods Enzymol. 1990;187:544–553. doi: 10.1016/0076-6879(90)87061-7. [DOI] [PubMed] [Google Scholar]
  28. Simonson M. S., Herman W. H. Protein kinase C and protein tyrosine kinase activity contribute to mitogenic signaling by endothelin-1. Cross-talk between G protein-coupled receptors and pp60c-src. J Biol Chem. 1993 May 5;268(13):9347–9357. [PubMed] [Google Scholar]
  29. Simonson M. S., Jones J. M., Dunn M. J. Differential regulation of fos and jun gene expression and AP-1 cis-element activity by endothelin isopeptides. Possible implications for mitogenic signaling by endothelin. J Biol Chem. 1992 Apr 25;267(12):8643–8649. [PubMed] [Google Scholar]
  30. Simonson M. S., Wann S., Mené P., Dubyak G. R., Kester M., Nakazato Y., Sedor J. R., Dunn M. J. Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells. J Clin Invest. 1989 Feb;83(2):708–712. doi: 10.1172/JCI113935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Simonson M. S., Wolfe J. A., Konieczkowski M., Sedor J. R., Dunn M. J. Regulation of prostaglandin endoperoxide synthase gene expression in cultured rat mesangial cells: induction by serum via a protein kinase-C-dependent mechanism. Mol Endocrinol. 1991 Mar;5(3):441–451. doi: 10.1210/mend-5-3-441. [DOI] [PubMed] [Google Scholar]
  32. Sun X. H., Copeland N. G., Jenkins N. A., Baltimore D. Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of helix-loop-helix proteins. Mol Cell Biol. 1991 Nov;11(11):5603–5611. doi: 10.1128/mcb.11.11.5603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Van Heyningen V., Hastie N. D. Wilms' tumour: reconciling genetics and biology. Trends Genet. 1992 Jan;8(1):16–21. doi: 10.1016/0168-9525(92)90019-z. [DOI] [PubMed] [Google Scholar]
  34. Weintraub H., Davis R., Tapscott S., Thayer M., Krause M., Benezra R., Blackwell T. K., Turner D., Rupp R., Hollenberg S. The myoD gene family: nodal point during specification of the muscle cell lineage. Science. 1991 Feb 15;251(4995):761–766. doi: 10.1126/science.1846704. [DOI] [PubMed] [Google Scholar]
  35. Wilson R. B., Kiledjian M., Shen C. P., Benezra R., Zwollo P., Dymecki S. M., Desiderio S. V., Kadesch T. Repression of immunoglobulin enhancers by the helix-loop-helix protein Id: implications for B-lymphoid-cell development. Mol Cell Biol. 1991 Dec;11(12):6185–6191. doi: 10.1128/mcb.11.12.6185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Witzgall R., O'Leary E., Gessner R., Ouellette A. J., Bonventre J. V. Kid-1, a putative renal transcription factor: regulation during ontogeny and in response to ischemia and toxic injury. Mol Cell Biol. 1993 Mar;13(3):1933–1942. doi: 10.1128/mcb.13.3.1933. [DOI] [PMC free article] [PubMed] [Google Scholar]

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