Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1985 Nov 11;13(21):7781–7793. doi: 10.1093/nar/13.21.7781

DNA sequences regulating human beta globin gene expression.

K A Kosche, C Dobkin, A Bank
PMCID: PMC322086  PMID: 2999704

Abstract

Human delta globin is expressed at approximately 1-2% of the level of human beta globin in erythroid cells despite the marked homology between these two globins. To determine the DNA sequences responsible for this effect, delta and beta globin genes and fusion products of these genes constructed in vitro were transfected and expressed in HeLa cells. The results indicate that when the small intervening sequence of the beta gene (beta IVS 1) is replaced by delta IVS 1, expression of the chimeric gene is the same as that of the normal beta globin gene. By contrast, when the large intervening sequence of the beta gene (beta IVS 2) is replaced by delta IVS 2, expression of the chimeric gene is markedly reduced. These results suggest that there are signals within IVS 2 of the delta and beta genes which affect their relative expression.

Full text

PDF
7782

Images in this article

Selected References

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

  1. Banerji J., Rusconi S., Schaffner W. Expression of a beta-globin gene is enhanced by remote SV40 DNA sequences. Cell. 1981 Dec;27(2 Pt 1):299–308. doi: 10.1016/0092-8674(81)90413-x. [DOI] [PubMed] [Google Scholar]
  2. Bank A., Mears J. G., Ramirez F. Disorders of human hemoglobin. Science. 1980 Feb 1;207(4430):486–493. doi: 10.1126/science.7352255. [DOI] [PubMed] [Google Scholar]
  3. Busslinger M., Moschonas N., Flavell R. A. Beta + thalassemia: aberrant splicing results from a single point mutation in an intron. Cell. 1981 Dec;27(2 Pt 1):289–298. doi: 10.1016/0092-8674(81)90412-8. [DOI] [PubMed] [Google Scholar]
  4. Dobkin C., Pergolizzi R. G., Bahre P., Bank A. Abnormal splice in a mutant human beta-globin gene not at the site of a mutation. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1184–1188. doi: 10.1073/pnas.80.5.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fukumaki Y., Ghosh P. K., Benz E. J., Jr, Reddy V. B., Lebowitz P., Forget B. G., Weissman S. M. Abnormally spliced messenger RNA in erythroid cells from patients with beta+ thalassemia and monkey cells expressing a cloned beta+-thalassemic gene. Cell. 1982 Mar;28(3):585–593. doi: 10.1016/0092-8674(82)90213-6. [DOI] [PubMed] [Google Scholar]
  6. Humphries R. K., Ley T., Turner P., Moulton A. D., Nienhuis A. W. Differences in human alpha-, beta- and delta-globin gene expression in monkey kidney cells. Cell. 1982 Aug;30(1):173–183. doi: 10.1016/0092-8674(82)90023-x. [DOI] [PubMed] [Google Scholar]
  7. Kimura A., Ohta Y., Fukumaki Y., Takagi Y. A fusion gene in man: DNA sequence analysis of the abnormal globin gene of hemoglobin Miyada. Biochem Biophys Res Commun. 1984 Mar 30;119(3):968–974. doi: 10.1016/0006-291x(84)90868-4. [DOI] [PubMed] [Google Scholar]
  8. Manley J. L. Accurate and specific polyadenylation of mRNA precursors in a soluble whole-cell lysate. Cell. 1983 Jun;33(2):595–605. doi: 10.1016/0092-8674(83)90440-3. [DOI] [PubMed] [Google Scholar]
  9. Mellon P., Parker V., Gluzman Y., Maniatis T. Identification of DNA sequences required for transcription of the human alpha 1-globin gene in a new SV40 host-vector system. Cell. 1981 Dec;27(2 Pt 1):279–288. doi: 10.1016/0092-8674(81)90411-6. [DOI] [PubMed] [Google Scholar]
  10. Miller C. W., Young K., Dumenil D., Alter B. P., Schofield J. M., Bank A. Specific globin mRNAs in human erythroleukemia (K562) cells. Blood. 1984 Jan;63(1):195–200. [PubMed] [Google Scholar]
  11. Orkin S. H., Sexton J. P., Cheng T. C., Goff S. C., Giardina P. J., Lee J. I., Kazazian H. H., Jr ATA box transcription mutation in beta-thalassemia. Nucleic Acids Res. 1983 Jul 25;11(14):4727–4734. doi: 10.1093/nar/11.14.4727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ramirez F., Mears J. G., Nudel U., Bank A., Luzzatto L., DiPrisco G., D'Avino R., Pepe G., Camardella L., Gambino R. Defects in DNA and globin messenger RNA in homozygotes for hemoglobin Lepore. J Clin Invest. 1979 Apr;63(4):736–742. doi: 10.1172/JCI109357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Zoller M. J., Smith M. Oligonucleotide-directed mutagenesis using M13-derived vectors: an efficient and general procedure for the production of point mutations in any fragment of DNA. Nucleic Acids Res. 1982 Oct 25;10(20):6487–6500. doi: 10.1093/nar/10.20.6487. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES