Abstract
The chicken adult alpha-globin genes, alpha A and alpha D, are closely linked in chromosomal DNA and are coordinately expressed in vivo in an approximate 3:1 ratio, respectively. When subcloned DNAs containing one or the other gene are stably transfected into QT6 quail fibroblasts, the alpha A-globin gene is expressed at measurable RNA levels, but the alpha D gene is not. The alpha A gene expression can be considerably increased by the presence of a linked Rous sarcoma virus long terminal repeat enhancer, but that of the alpha D gene remains undetectable. Transfection with subclones containing both genes, either in cis or in trans, leads to considerably reduced alpha A RNA levels and still no observable alpha D gene expression. Transfection with deleted subclones suggests that maximal expression levels in this system require the alpha A-globin gene promoter, as opposed to that of the alpha D gene, but that such expression is greatly reduced by one or more DNA sequences which lie approximately 2,000 base pairs upstream of the alpha A gene, within the body of the alpha D gene.
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- 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]
- Atweh G. F., Liu J. M., Brickner H. E., Zhu X. X. A silencer element from the alpha-globin gene inhibits expression of beta-like genes. Mol Cell Biol. 1988 Nov;8(11):5047–5051. doi: 10.1128/mcb.8.11.5047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ayer S., Benyajati C. Conserved enhancer and silencer elements responsible for differential Adh transcription in Drosophila cell lines. Mol Cell Biol. 1990 Jul;10(7):3512–3523. doi: 10.1128/mcb.10.7.3512. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Behringer R. R., Hammer R. E., Brinster R. L., Palmiter R. D., Townes T. M. Two 3' sequences direct adult erythroid-specific expression of human beta-globin genes in transgenic mice. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7056–7060. doi: 10.1073/pnas.84.20.7056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Behringer R. R., Ryan T. M., Palmiter R. D., Brinster R. L., Townes T. M. Human gamma- to beta-globin gene switching in transgenic mice. Genes Dev. 1990 Mar;4(3):380–389. doi: 10.1101/gad.4.3.380. [DOI] [PubMed] [Google Scholar]
- Behringer R. R., Ryan T. M., Palmiter R. D., Brinster R. L., Townes T. M. Human gamma- to beta-globin gene switching in transgenic mice. Genes Dev. 1990 Mar;4(3):380–389. doi: 10.1101/gad.4.3.380. [DOI] [PubMed] [Google Scholar]
- Beug H., Palmieri S., Freudenstein C., Zentgraf H., Graf T. Hormone-dependent terminal differentiation in vitro of chicken erythroleukemia cells transformed by ts mutants of avian erythroblastosis virus. Cell. 1982 Apr;28(4):907–919. doi: 10.1016/0092-8674(82)90070-8. [DOI] [PubMed] [Google Scholar]
- Blom van Assendelft G., Hanscombe O., Grosveld F., Greaves D. R. The beta-globin dominant control region activates homologous and heterologous promoters in a tissue-specific manner. Cell. 1989 Mar 24;56(6):969–977. doi: 10.1016/0092-8674(89)90630-2. [DOI] [PubMed] [Google Scholar]
- Brand A. H., Breeden L., Abraham J., Sternglanz R., Nasmyth K. Characterization of a "silencer" in yeast: a DNA sequence with properties opposite to those of a transcriptional enhancer. Cell. 1985 May;41(1):41–48. doi: 10.1016/0092-8674(85)90059-5. [DOI] [PubMed] [Google Scholar]
- Brown J. L., Ingram V. M. Structural studies on chick embryonic hemoglobins. J Biol Chem. 1974 Jun 25;249(12):3960–3972. [PubMed] [Google Scholar]
- Brush D., Dodgson J. B., Choi O. R., Stevens P. W., Engel J. D. Replacement variant histone genes contain intervening sequences. Mol Cell Biol. 1985 Jun;5(6):1307–1317. doi: 10.1128/mcb.5.6.1307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Cao S. X., Gutman P. D., Dave H. P., Schechter A. N. Identification of a transcriptional silencer in the 5'-flanking region of the human epsilon-globin gene. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5306–5309. doi: 10.1073/pnas.86.14.5306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Choi O. R., Engel J. D. A 3' enhancer is required for temporal and tissue-specific transcriptional activation of the chicken adult beta-globin gene. Nature. 1986 Oct 23;323(6090):731–734. doi: 10.1038/323731a0. [DOI] [PubMed] [Google Scholar]
- Choi O. R., Engel J. D. Developmental regulation of beta-globin gene switching. Cell. 1988 Oct 7;55(1):17–26. doi: 10.1016/0092-8674(88)90005-0. [DOI] [PubMed] [Google Scholar]
- Cowie A., Myers R. M. DNA sequences involved in transcriptional regulation of the mouse beta-globin promoter in murine erythroleukemia cells. Mol Cell Biol. 1988 Aug;8(8):3122–3128. doi: 10.1128/mcb.8.8.3122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Dodgson J. B., Engel J. D. The nucleotide sequence of the adult chicken alpha-globin genes. J Biol Chem. 1983 Apr 10;258(7):4623–4629. [PubMed] [Google Scholar]
- Dodgson J. B., McCune K. C., Rusling D. J., Krust A., Engel J. D. Adult chicken alpha-globin genes alpha A and alpha D: no anemic shock alpha-globin exists in domestic chickens. Proc Natl Acad Sci U S A. 1981 Oct;78(10):5998–6002. doi: 10.1073/pnas.78.10.5998. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Efstratiadis A., Posakony J. W., Maniatis T., Lawn R. M., O'Connell C., Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M., Slightom J. L. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653–668. doi: 10.1016/0092-8674(80)90429-8. [DOI] [PubMed] [Google Scholar]
- Emerson B. M., Nickol J. M., Jackson P. D., Felsenfeld G. Analysis of the tissue-specific enhancer at the 3' end of the chicken adult beta-globin gene. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4786–4790. doi: 10.1073/pnas.84.14.4786. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Engel J. D., Rusling D. J., McCune K. C., Dodgson J. B. Unusual structure of the chicken embryonic alpha-globin gene, pi'. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1392–1396. doi: 10.1073/pnas.80.5.1392. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Engel J. D., Sugarman B. J., Dodgson J. B. A chicken histone H3 gene contains intervening sequences. Nature. 1982 Jun 3;297(5865):434–436. doi: 10.1038/297434a0. [DOI] [PubMed] [Google Scholar]
- Enver T., Raich N., Ebens A. J., Papayannopoulou T., Costantini F., Stamatoyannopoulos G. Developmental regulation of human fetal-to-adult globin gene switching in transgenic mice. Nature. 1990 Mar 22;344(6264):309–313. doi: 10.1038/344309a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Farrell F. X., Sax C. M., Zehner Z. E. A negative element involved in vimentin gene expression. Mol Cell Biol. 1990 May;10(5):2349–2358. doi: 10.1128/mcb.10.5.2349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fischer H. D., Dodgson J. B., Hughes S., Engel J. D. An unusual 5' splice sequence is efficiently utilized in vivo. Proc Natl Acad Sci U S A. 1984 May;81(9):2733–2737. doi: 10.1073/pnas.81.9.2733. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forrester W. C., Epner E., Driscoll M. C., Enver T., Brice M., Papayannopoulou T., Groudine M. A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus. Genes Dev. 1990 Oct;4(10):1637–1649. doi: 10.1101/gad.4.10.1637. [DOI] [PubMed] [Google Scholar]
- Grosveld G. C., de Boer E., Shewmaker C. K., Flavell R. A. DNA sequences necessary for transcription of the rabbit beta-globin gene in vivo. Nature. 1982 Jan 14;295(5845):120–126. doi: 10.1038/295120a0. [DOI] [PubMed] [Google Scholar]
- Herbst R. S., Friedman N., Darnell J. E., Jr, Babiss L. E. Positive and negative regulatory elements in the mouse albumin enhancer. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1553–1557. doi: 10.1073/pnas.86.5.1553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hesse J. E., Nickol J. M., Lieber M. R., Felsenfeld G. Regulated gene expression in transfected primary chicken erythrocytes. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4312–4316. doi: 10.1073/pnas.83.12.4312. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jackson P. D., Evans T., Nickol J. M., Felsenfeld G. Developmental modulation of protein binding to beta-globin gene regulatory sites within chicken erythrocyte nuclei. Genes Dev. 1989 Dec;3(12A):1860–1873. doi: 10.1101/gad.3.12a.1860. [DOI] [PubMed] [Google Scholar]
- Knezetic J. A., Felsenfeld G. Identification and characterization of a chicken alpha-globin enhancer. Mol Cell Biol. 1989 Mar;9(3):893–901. doi: 10.1128/mcb.9.3.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kollias G., Wrighton N., Hurst J., Grosveld F. Regulated expression of human A gamma-, beta-, and hybrid gamma beta-globin genes in transgenic mice: manipulation of the developmental expression patterns. Cell. 1986 Jul 4;46(1):89–94. doi: 10.1016/0092-8674(86)90862-7. [DOI] [PubMed] [Google Scholar]
- Larsen P. R., Harney J. W., Moore D. D. Repression mediates cell-type-specific expression of the rat growth hormone gene. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8283–8287. doi: 10.1073/pnas.83.21.8283. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moscovici C., Moscovici M. G., Jimenez H., Lai M. M., Hayman M. J., Vogt P. K. Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Cell. 1977 May;11(1):95–103. doi: 10.1016/0092-8674(77)90320-8. [DOI] [PubMed] [Google Scholar]
- Myers R. M., Tilly K., Maniatis T. Fine structure genetic analysis of a beta-globin promoter. Science. 1986 May 2;232(4750):613–618. doi: 10.1126/science.3457470. [DOI] [PubMed] [Google Scholar]
- Ngai J., Bond V. C., Wold B. J., Lazarides E. Expression of transfected vimentin genes in differentiating murine erythroleukemia cells reveals divergent cis-acting regulation of avian and mammalian vimentin sequences. Mol Cell Biol. 1987 Nov;7(11):3955–3970. doi: 10.1128/mcb.7.11.3955. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nickol J. M., Felsenfeld G. Bidirectional control of the chicken beta- and epsilon-globin genes by a shared enhancer. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2548–2552. doi: 10.1073/pnas.85.8.2548. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robins D. M., Ripley S., Henderson A. S., Axel R. Transforming DNA integrates into the host chromosome. Cell. 1981 Jan;23(1):29–39. doi: 10.1016/0092-8674(81)90267-1. [DOI] [PubMed] [Google Scholar]
- Ryan T. M., Behringer R. R., Townes T. M., Palmiter R. D., Brinster R. L. High-level erythroid expression of human alpha-globin genes in transgenic mice. Proc Natl Acad Sci U S A. 1989 Jan;86(1):37–41. doi: 10.1073/pnas.86.1.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shore D., Nasmyth K. Purification and cloning of a DNA binding protein from yeast that binds to both silencer and activator elements. Cell. 1987 Dec 4;51(5):721–732. doi: 10.1016/0092-8674(87)90095-x. [DOI] [PubMed] [Google Scholar]
- Smith D. R., Calvo J. M. Nucleotide sequence of the E coli gene coding for dihydrofolate reductase. Nucleic Acids Res. 1980 May 24;8(10):2255–2274. doi: 10.1093/nar/8.10.2255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Talbot D., Collis P., Antoniou M., Vidal M., Grosveld F., Greaves D. R. A dominant control region from the human beta-globin locus conferring integration site-independent gene expression. Nature. 1989 Mar 23;338(6213):352–355. doi: 10.1038/338352a0. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Trudel M., Magram J., Bruckner L., Costantini F. Upstream G gamma-globin and downstream beta-globin sequences required for stage-specific expression in transgenic mice. Mol Cell Biol. 1987 Nov;7(11):4024–4029. doi: 10.1128/mcb.7.11.4024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsai S. F., Martin D. I., Zon L. I., D'Andrea A. D., Wong G. G., Orkin S. H. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature. 1989 Jun 8;339(6224):446–451. doi: 10.1038/339446a0. [DOI] [PubMed] [Google Scholar]
- Weintraub H., Beug H., Groudine M., Graf T. Temperature-sensitive changes in the structure of globin chromatin in lines of red cell precursors transformed by ts-AEV. Cell. 1982 Apr;28(4):931–940. doi: 10.1016/0092-8674(82)90072-1. [DOI] [PubMed] [Google Scholar]
- Whelan J., Poon D., Weil P. A., Stein R. Pancreatic beta-cell-type-specific expression of the rat insulin II gene is controlled by positive and negative cellular transcriptional elements. Mol Cell Biol. 1989 Aug;9(8):3253–3259. doi: 10.1128/mcb.9.8.3253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Yamamoto M., Ko L. J., Leonard M. W., Beug H., Orkin S. H., Engel J. D. Activity and tissue-specific expression of the transcription factor NF-E1 multigene family. Genes Dev. 1990 Oct;4(10):1650–1662. doi: 10.1101/gad.4.10.1650. [DOI] [PubMed] [Google Scholar]
- Yoshihara C. M., Lee J. D., Dodgson J. B. The chicken carbonic anhydrase II gene: evidence for a recent shift in intron position. Nucleic Acids Res. 1987 Jan 26;15(2):753–770. doi: 10.1093/nar/15.2.753. [DOI] [PMC free article] [PubMed] [Google Scholar]