Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Sep;86(17):6548–6552. doi: 10.1073/pnas.86.17.6548

Cis- and trans-acting elements involved in the regulation of the erythroid promoter of the human porphobilinogen deaminase gene.

V Mignotte 1, J F Eleouet 1, N Raich 1, P H Romeo 1
PMCID: PMC297881  PMID: 2771941

Abstract

Two cis-acting sequences, recognized by two erythroid-specific trans-acting factors, are involved in the regulation of the erythroid promoter of the human gene coding for porphobilinogen deaminase (PBGD). The first region, located at -70, binds the erythroid factor NF-E1, and point mutations within this region abolish the induction of transcription of this promoter during murine erythroleukemia (MEL) cell differentiation. The second region, located at -160, binds the erythroid-specific factor NF-E2 and the ubiquitous factor AP1. Using UV cross-linking, we show that NF-E2 has a higher molecular weight than AP1, demonstrating that NF-E2 is not an erythroid-specific degradation product of AP1. By point mutagenesis of the NF-E2/AP1 binding site, we define mutations that abolish binding of either NF-E2 alone or AP1 and NF-E2 together. Regulation of transcription of the PBGD erythroid promoter is abolished by those mutations, suggesting that NF-E2 but not AP1 is necessary for correct regulation of this promoter in erythroid cells.

Full text

PDF
6548

Images in this article

6549Image
on p.6549
6550Image
on p.6550
6550Image
on p.6550
6551Image
on p.6551
6551Image
on p.6551

Selected References

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

  1. Antoniou M., deBoer E., Habets G., Grosveld F. The human beta-globin gene contains multiple regulatory regions: identification of one promoter and two downstream enhancers. EMBO J. 1988 Feb;7(2):377–384. doi: 10.1002/j.1460-2075.1988.tb02824.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cereghini S., Raymondjean M., Carranca A. G., Herbomel P., Yaniv M. Factors involved in control of tissue-specific expression of albumin gene. Cell. 1987 Aug 14;50(4):627–638. doi: 10.1016/0092-8674(87)90036-5. [DOI] [PubMed] [Google Scholar]
  3. Charnay P., Treisman R., Mellon P., Chao M., Axel R., Maniatis T. Differences in human alpha- and beta-globin gene expression in mouse erythroleukemia cells: the role of intragenic sequences. Cell. 1984 Aug;38(1):251–263. doi: 10.1016/0092-8674(84)90547-6. [DOI] [PubMed] [Google Scholar]
  4. Chretien S., Dubart A., Beaupain D., Raich N., Grandchamp B., Rosa J., Goossens M., Romeo P. H. Alternative transcription and splicing of the human porphobilinogen deaminase gene result either in tissue-specific or in housekeeping expression. Proc Natl Acad Sci U S A. 1988 Jan;85(1):6–10. doi: 10.1073/pnas.85.1.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Courtois G., Baumhueter S., Crabtree G. R. Purified hepatocyte nuclear factor 1 interacts with a family of hepatocyte-specific promoters. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7937–7941. doi: 10.1073/pnas.85.21.7937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dostatni N., Thierry F., Yaniv M. A dimer of BPV-1 E2 containing a protease resistant core interacts with its DNA target. EMBO J. 1988 Dec 1;7(12):3807–3816. doi: 10.1002/j.1460-2075.1988.tb03265.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans T., Reitman M., Felsenfeld G. An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5976–5980. doi: 10.1073/pnas.85.16.5976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grosveld F., van Assendelft G. B., Greaves D. R., Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. doi: 10.1016/0092-8674(87)90584-8. [DOI] [PubMed] [Google Scholar]
  10. Hattori K., Angel P., Le Beau M. M., Karin M. Structure and chromosomal localization of the functional intronless human JUN protooncogene. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9148–9152. doi: 10.1073/pnas.85.23.9148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jackson S. P., Tjian R. O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation. Cell. 1988 Oct 7;55(1):125–133. doi: 10.1016/0092-8674(88)90015-3. [DOI] [PubMed] [Google Scholar]
  12. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McKnight S., Tjian R. Transcriptional selectivity of viral genes in mammalian cells. Cell. 1986 Sep 12;46(6):795–805. doi: 10.1016/0092-8674(86)90061-9. [DOI] [PubMed] [Google Scholar]
  14. Mignotte V., Wall L., deBoer E., Grosveld F., Romeo P. H. Two tissue-specific factors bind the erythroid promoter of the human porphobilinogen deaminase gene. Nucleic Acids Res. 1989 Jan 11;17(1):37–54. doi: 10.1093/nar/17.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Noguchi T., Yamada K., Inoue H., Matsuda T., Tanaka T. The L- and R-type isozymes of rat pyruvate kinase are produced from a single gene by use of different promoters. J Biol Chem. 1987 Oct 15;262(29):14366–14371. [PubMed] [Google Scholar]
  16. Plumb M., Frampton J., Wainwright H., Walker M., Macleod K., Goodwin G., Harrison P. GATAAG; a cis-control region binding an erythroid-specific nuclear factor with a role in globin and non-globin gene expression. Nucleic Acids Res. 1989 Jan 11;17(1):73–92. doi: 10.1093/nar/17.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Raich N., Mignotte V., Dubart A., Beaupain D., Leboulch P., Romana M., Chabret C., Charnay P., Papayannopoulou T., Goossens M. Regulated expression of the overlapping ubiquitous and erythroid transcription units of the human porphobilinogen deaminase (PBG-D) gene introduced into non-erythroid and erythroid cells. J Biol Chem. 1989 Jun 15;264(17):10186–10192. [PubMed] [Google Scholar]
  18. Raich N., Romeo P. H., Dubart A., Beaupain D., Cohen-Solal M., Goossens M. Molecular cloning and complete primary sequence of human erythrocyte porphobilinogen deaminase. Nucleic Acids Res. 1986 Aug 11;14(15):5955–5968. doi: 10.1093/nar/14.15.5955. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reitman M., Felsenfeld G. Mutational analysis of the chicken beta-globin enhancer reveals two positive-acting domains. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6267–6271. doi: 10.1073/pnas.85.17.6267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Roméo P. H., Raich N., Dubart A., Beaupain D., Pryor M., Kushner J., Cohen-Solal M., Goossens M. Molecular cloning and nucleotide sequence of a complete human uroporphyrinogen decarboxylase cDNA. J Biol Chem. 1986 Jul 25;261(21):9825–9831. [PubMed] [Google Scholar]
  21. Schoenhaut D. S., Curtis P. J. Nucleotide sequence of mouse 5-aminolevulinic acid synthase cDNA and expression of its gene in hepatic and erythroid tissues. Gene. 1986;48(1):55–63. doi: 10.1016/0378-1119(86)90351-3. [DOI] [PubMed] [Google Scholar]
  22. Schüle R., Muller M., Otsuka-Murakami H., Renkawitz R. Cooperativity of the glucocorticoid receptor and the CACCC-box binding factor. Nature. 1988 Mar 3;332(6159):87–90. doi: 10.1038/332087a0. [DOI] [PubMed] [Google Scholar]
  23. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
  24. Wall L., deBoer E., Grosveld F. The human beta-globin gene 3' enhancer contains multiple binding sites for an erythroid-specific protein. Genes Dev. 1988 Sep;2(9):1089–1100. doi: 10.1101/gad.2.9.1089. [DOI] [PubMed] [Google Scholar]
  25. Wright S., Rosenthal A., Flavell R., Grosveld F. DNA sequences required for regulated expression of beta-globin genes in murine erythroleukemia cells. Cell. 1984 Aug;38(1):265–273. doi: 10.1016/0092-8674(84)90548-8. [DOI] [PubMed] [Google Scholar]
  26. deBoer E., Antoniou M., Mignotte V., Wall L., Grosveld F. The human beta-globin promoter; nuclear protein factors and erythroid specific induction of transcription. EMBO J. 1988 Dec 20;7(13):4203–4212. doi: 10.1002/j.1460-2075.1988.tb03317.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES