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. 1987 May 11;15(9):3671–3688. doi: 10.1093/nar/15.9.3671

Changes in minor transcripts from the alpha 1 and beta maj globin and glutathione peroxidase genes during erythropoiesis.

J Frampton, D Conkie, I Chambers, W McBain, M Dexter, P Harrison
PMCID: PMC340775  PMID: 3473445

Abstract

We have analysed the transcriptional regulation of the murine alpha 1 and beta maj globin genes and the glutathione peroxidase (GSHPx) gene, which are all highly expressed during erythropoiesis. The levels of minor RNAs compared to the major message were monitored throughout differentiation within the erythroid lineage. For each gene, upstream transcripts arise from distinct clusters of sites which are regulated differently during differentiation: some occur only during early erythropoiesis, some occur early and persist to the terminal stages, while others accumulate later and roughly in parallel with the main RNA transcript. In addition, opposite strand transcripts from the GSHPx gene were found in increasing amounts during later stages of erythropoiesis. The initiation sites for specific subsets of these minor transcripts lie close to sequences known to be involved in globin gene regulation (i.e. the TATA, CAAT and the CACCCT boxes) or other conserved sequences; others lie close to developmentally regulated DNase I hypersensitive sites around the globin and GSHPx genes.

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Selected References

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  1. Affara N., Fleming J., Goldfarb P. S., Black E., Thiele B., Harrison P. R. Analysis of chromatin changes associated with the expression of globin and non-globin genes in cell hybrids between erythroid and other cells. Nucleic Acids Res. 1985 Aug 12;13(15):5629–5644. doi: 10.1093/nar/13.15.5629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alan M., Grindlay G. J., Stefani L., Paul J. Epsilon globin gene transcripts originating upstream of the mRNA cap site in K562 cells and normal human embryos. Nucleic Acids Res. 1982 Sep 11;10(17):5133–5147. doi: 10.1093/nar/10.17.5133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Allan M., Lanyon W. G., Paul J. Multiple origins of transcription in the 4.5 Kb upstream of the epsilon-globin gene. Cell. 1983 Nov;35(1):187–197. doi: 10.1016/0092-8674(83)90221-0. [DOI] [PubMed] [Google Scholar]
  4. Allan M., Montague P., Grindlay G. J., Sibbet G., Donovan-Peluso M., Bank A., Paul J. Tissue specific transcription of the human epsilon-globin gene following transfection into the embryonic erythroid cell line K562. Nucleic Acids Res. 1985 Sep 11;13(17):6125–6136. doi: 10.1093/nar/13.17.6125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Allan M., Paul J. Transcription in vivo of an Alu family member upstream from the human epsilon-globin gene. Nucleic Acids Res. 1984 Jan 25;12(2):1193–1200. doi: 10.1093/nar/12.2.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Allan M., Zhu J. D., Montague P., Paul J. Differential response of multiple epsilon-globin cap sites to cis- and trans-acting controls. Cell. 1984 Sep;38(2):399–407. doi: 10.1016/0092-8674(84)90495-1. [DOI] [PubMed] [Google Scholar]
  7. Carlson D. P., Ross J. Human beta-globin promoter and coding sequences transcribed by RNA polymerase III. Cell. 1983 Oct;34(3):857–864. doi: 10.1016/0092-8674(83)90543-3. [DOI] [PubMed] [Google Scholar]
  8. Carlson D. P., Ross J. Point mutation associated with hereditary persistence of fetal hemoglobin decreases RNA polymerase III transcription upstream of the affected gamma-globin gene. Mol Cell Biol. 1986 Sep;6(9):3278–3282. doi: 10.1128/mcb.6.9.3278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carlson D. P., Ross J. alpha-Amanitin-insensitive transcription of mouse beta major-globin 5'-flanking and structural gene sequences correlates with mRNA expression. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7782–7786. doi: 10.1073/pnas.81.24.7782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chada K., Magram J., Raphael K., Radice G., Lacy E., Costantini F. Specific expression of a foreign beta-globin gene in erythroid cells of transgenic mice. 1985 Mar 28-Apr 3Nature. 314(6009):377–380. doi: 10.1038/314377a0. [DOI] [PubMed] [Google Scholar]
  11. Chambers I., Frampton J., Goldfarb P., Affara N., McBain W., Harrison P. R. The structure of the mouse glutathione peroxidase gene: the selenocysteine in the active site is encoded by the 'termination' codon, TGA. EMBO J. 1986 Jun;5(6):1221–1227. doi: 10.1002/j.1460-2075.1986.tb04350.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chang D. D., Hixson J. E., Clayton D. A. Minor transcription initiation events indicate that both human mitochondrial promoters function bidirectionally. Mol Cell Biol. 1986 Jan;6(1):294–301. doi: 10.1128/mcb.6.1.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chao M. V., Mellon P., Charnay P., Maniatis T., Axel R. The regulated expression of beta-globin genes introduced into mouse erythroleukemia cells. Cell. 1983 Feb;32(2):483–493. doi: 10.1016/0092-8674(83)90468-3. [DOI] [PubMed] [Google Scholar]
  14. Charnay P., Mellon P., Maniatis T. Linker scanning mutagenesis of the 5'-flanking region of the mouse beta-major-globin gene: sequence requirements for transcription in erythroid and nonerythroid cells. Mol Cell Biol. 1985 Jun;5(6):1498–1511. doi: 10.1128/mcb.5.6.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Contreras R., Gheysen D., Knowland J., van de Voorde A., Fiers W. Evidence for the direct involvement of DNA replication origin in synthesis of late SV40 RNA. Nature. 1982 Dec 9;300(5892):500–505. doi: 10.1038/300500a0. [DOI] [PubMed] [Google Scholar]
  17. Dexter T. M., Garland J., Scott D., Scolnick E., Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. doi: 10.1084/jem.152.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Dierks P., van Ooyen A., Cochran M. D., Dobkin C., Reiser J., Weissmann C. Three regions upstream from the cap site are required for efficient and accurate transcription of the rabbit beta-globin gene in mouse 3T6 cells. Cell. 1983 Mar;32(3):695–706. doi: 10.1016/0092-8674(83)90055-7. [DOI] [PubMed] [Google Scholar]
  19. Ghosh P. K., Lebowitz P. Simian virus 40 early mRNA's contain multiple 5' termini upstream and downstream from a Hogness-Goldberg sequence; a shift in 5' termini during the lytic cycle is mediated by large T antigen. J Virol. 1981 Oct;40(1):224–240. doi: 10.1128/jvi.40.1.224-240.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gilmour R. S., Spandidos D. A., Vass J. K., Gow J. W., Paul J. A negative regulatory sequence near the mouse beta-maj globin gene associated with a region of potential Z-DNA. EMBO J. 1984 Jun;3(6):1263–1272. doi: 10.1002/j.1460-2075.1984.tb01961.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Grindlay G. J., Lanyon W. G., Allan M., Paul J. Alternative sites of transcription initiation upstream of the canonical cap site in human gamma-globin and beta-globin genes. Nucleic Acids Res. 1984 Feb 24;12(4):1811–1820. doi: 10.1093/nar/12.4.1811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hess J., Perez-Stable C., Deisseroth A., Shen C. K. Characterization of an unique RNA initiated immediately upstream from human alpha 1 globin gene in vivo and in vitro: polymerase II-dependence, tissue specificity, and subcellular location. Nucleic Acids Res. 1985 Sep 11;13(17):6059–6074. doi: 10.1093/nar/13.17.6059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Iscove N. N., Sieber F. Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture. Exp Hematol. 1975 Jan;3(1):32–43. [PubMed] [Google Scholar]
  25. Jahn C. L., Hutchison C. A., 3rd, Phillips S. J., Weaver S., Haigwood N. L., Voliva C. F., Edgell M. H. DNA sequence organization of the beta-globin complex in the BALB/c mouse. Cell. 1980 Aug;21(1):159–168. doi: 10.1016/0092-8674(80)90123-3. [DOI] [PubMed] [Google Scholar]
  26. Kaneda T., Murate T., Sheffery M., Brown K., Rifkind R. A., Marks P. A. Gene expression during terminal differentiation: dexamethasone suppression of inducer-mediated alpha 1- and beta maj-globin gene expression. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5020–5024. doi: 10.1073/pnas.82.15.5020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kollias G., Sekeris C. E., Grosveld F. G. Alpha-amanitin insensitive transcription of the human epsilon-globin gene. Nucleic Acids Res. 1985 Nov 25;13(22):7993–8005. doi: 10.1093/nar/13.22.7993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Konkel D. A., Maizel J. V., Jr, Leder P. The evolution and sequence comparison of two recently diverged mouse chromosomal beta--globin genes. Cell. 1979 Nov;18(3):865–873. doi: 10.1016/0092-8674(79)90138-7. [DOI] [PubMed] [Google Scholar]
  29. Mitchell P. J., Carothers A. M., Han J. H., Harding J. D., Kas E., Venolia L., Chasin L. A. Multiple transcription start sites, DNase I-hypersensitive sites, and an opposite-strand exon in the 5' region of the CHO dhfr gene. Mol Cell Biol. 1986 Feb;6(2):425–440. doi: 10.1128/mcb.6.2.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Moschonas N., de Boer E., Flavell R. A. The DNA sequence of the 5' flanking region of the human beta-globin gene: evolutionary conservation and polymorphic differences. Nucleic Acids Res. 1982 Mar 25;10(6):2109–2120. doi: 10.1093/nar/10.6.2109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nijhof W., Wierenga P. K. Isolation and characterization of the erythroid progenitor cell: CFU-E. J Cell Biol. 1983 Feb;96(2):386–392. doi: 10.1083/jcb.96.2.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Nishioka Y., Leder P. The complete sequence of a chromosomal mouse alpha--globin gene reveals elements conserved throughout vertebrate evolution. Cell. 1979 Nov;18(3):875–882. doi: 10.1016/0092-8674(79)90139-9. [DOI] [PubMed] [Google Scholar]
  33. Osborne T. F., Berk A. J. Far upstream initiation sites for adenovirus early region 1A transcription are utilized after the onset of viral DNA replication. J Virol. 1983 Feb;45(2):594–599. doi: 10.1128/jvi.45.2.594-599.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rutherford T., Nienhuis A. W. Human globin gene promoter sequences are sufficient for specific expression of a hybrid gene transfected into tissue culture cells. Mol Cell Biol. 1987 Jan;7(1):398–402. doi: 10.1128/mcb.7.1.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sheffery M., Rifkind R. A., Marks P. A. Hexamethylenebisacetamide-resistant murine erythroleukemia cells have altered patterns of inducer-mediated chromatin changes. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3349–3353. doi: 10.1073/pnas.80.11.3349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Townes T. M., Lingrel J. B., Chen H. Y., Brinster R. L., Palmiter R. D. Erythroid-specific expression of human beta-globin genes in transgenic mice. EMBO J. 1985 Jul;4(7):1715–1723. doi: 10.1002/j.1460-2075.1985.tb03841.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Treisman R., Green M. R., Maniatis T. cis and trans activation of globin gene transcription in transient assays. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7428–7432. doi: 10.1073/pnas.80.24.7428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Venta P. J., Montgomery J. C., Hewett-Emmett D., Tashian R. E. Comparison of the 5' regions of human and mouse carbonic anhydrase II genes and identification of possible regulatory elements. Biochim Biophys Acta. 1985 Dec 18;826(4):195–201. doi: 10.1016/0167-4781(85)90006-5. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Wright S., deBoer E., Grosveld F. G., Flavell R. A. Regulated expression of the human beta-globin gene family in murine erythroleukaemia cells. Nature. 1983 Sep 22;305(5932):333–336. doi: 10.1038/305333a0. [DOI] [PubMed] [Google Scholar]
  41. Zhu J., Allan M., Paul J. The chromatin structure of the human epsilon globin gene: nuclease hypersensitive sites correlate with multiple initiation sites of transcription. Nucleic Acids Res. 1984 Dec 11;12(23):9191–9204. doi: 10.1093/nar/12.23.9191. [DOI] [PMC free article] [PubMed] [Google Scholar]

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