Abstract
We have analyzed the chromatin structure of the human beta-globin locus in somatic cell hybrids resulting from the fusion of human non-erythroid cells and mouse erythroleukemia (MEL) cells. In these hybrids, the human adult beta-globin gene, but neither the embryonic nor fetal globin genes, is activated transcriptionally. In addition, the DNase I-resistant beta-like globin locus characteristic of the parental non-erythroid human cells (1,2) is reorganized over an approximately 80 kb region, including the formation of the developmentally stable hypersensitive sites 50 kb 5' and 20 kg 3' of the activated adult beta-globin gene (2,3). These results are consistent with the hypothesis that events occurring at the 5' and/or 3' developmentally stable hypersensitive sites are important, if not necessary, for the activation of the beta-globin locus.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Andersson L. C., Nilsson K., Gahmberg C. G. K562--a human erythroleukemic cell line. Int J Cancer. 1979 Feb;23(2):143–147. doi: 10.1002/ijc.2910230202. [DOI] [PubMed] [Google Scholar]
- Baralle F. E., Shoulders C. C., Goodbourn S., Jeffreys A., Proudfoot N. J. The 5' flanking region of human epsilon-globin gene. Nucleic Acids Res. 1980 Oct 10;8(19):4393–4404. doi: 10.1093/nar/8.19.4393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baralle F. E., Shoulders C. C., Proudfoot N. J. The primary structure of the human epsilon-globin gene. Cell. 1980 Oct;21(3):621–626. doi: 10.1016/0092-8674(80)90425-0. [DOI] [PubMed] [Google Scholar]
- Camaschella C., Serra A., Saglio G., Baiget M., Malgaretti N., Mantovani R., Ottolenghi S. The 3' ends of the deletions of Spanish delta beta zero-thalassemia and black HPFH 1 and 2 lie within 17 kilobases. Blood. 1987 Aug;70(2):593–596. [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]
- Chiang Y. L., Ley T. J., Sanders-Haigh L., Anderson W. F. Human globin gene expression in hybrid 2S MEL X human fibroblast cells. Somat Cell Mol Genet. 1984 Jul;10(4):399–407. doi: 10.1007/BF01535635. [DOI] [PubMed] [Google Scholar]
- Collins S. J., Gallo R. C., Gallagher R. E. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. doi: 10.1038/270347a0. [DOI] [PubMed] [Google Scholar]
- Curtin P., Pirastu M., Kan Y. W., Gobert-Jones J. A., Stephens A. D., Lehmann H. A distant gene deletion affects beta-globin gene function in an atypical gamma delta beta-thalassemia. J Clin Invest. 1985 Oct;76(4):1554–1558. doi: 10.1172/JCI112136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Di Segni G., Carrara G., Tocchini-Valentini G. R., Shoulders C. C., Baralle F. E. Selective in vitro transcription of one of the two Alu family repeats present in the 5' flanking region of the human epsilon-globin gene. Nucleic Acids Res. 1981 Dec 21;9(24):6709–6722. doi: 10.1093/nar/9.24.6709. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Donovan-Peluso M., Young K., Dobkin C., Bank A. Erythroleukemia (K562) cells contain a functional beta-globin gene. Mol Cell Biol. 1984 Nov;4(11):2553–2555. doi: 10.1128/mcb.4.11.2553. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fordis C. M., Anagnou N. P., Dean A., Nienhuis A. W., Schechter A. N. A beta-globin gene, inactive in the K562 leukemic cell, functions normally in a heterologous expression system. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4485–4489. doi: 10.1073/pnas.81.14.4485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Forrester W. C., Thompson C., Elder J. T., Groudine M. A developmentally stable chromatin structure in the human beta-globin gene cluster. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1359–1363. doi: 10.1073/pnas.83.5.1359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Groudine M., Kohwi-Shigematsu T., Gelinas R., Stamatoyannopoulos G., Papayannopoulou T. Human fetal to adult hemoglobin switching: changes in chromatin structure of the beta-globin gene locus. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7551–7555. doi: 10.1073/pnas.80.24.7551. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karlsson S., Nienhuis A. W. Developmental regulation of human globin genes. Annu Rev Biochem. 1985;54:1071–1108. doi: 10.1146/annurev.bi.54.070185.005231. [DOI] [PubMed] [Google Scholar]
- Koeffler H. P., Golde D. W. Acute myelogenous leukemia: a human cell line responsive to colony-stimulating activity. Science. 1978 Jun 9;200(4346):1153–1154. doi: 10.1126/science.306682. [DOI] [PubMed] [Google Scholar]
- Koeffler H. P., Golde D. W. Human myeloid leukemia cell lines: a review. Blood. 1980 Sep;56(3):344–350. [PubMed] [Google Scholar]
- Kollias G., Hurst J., deBoer E., Grosveld F. The human beta-globin gene contains a downstream developmental specific enhancer. Nucleic Acids Res. 1987 Jul 24;15(14):5739–5747. doi: 10.1093/nar/15.14.5739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Li Q., Powers P. A., Smithies O. Nucleotide sequence of 16-kilobase pairs of DNA 5' to the human epsilon-globin gene. J Biol Chem. 1985 Dec 5;260(28):14901–14910. [PubMed] [Google Scholar]
- Linial M., Gunderson N., Groudine M. Enhanced transcription of c-myc in bursal lymphoma cells requires continuous protein synthesis. Science. 1985 Dec 6;230(4730):1126–1132. doi: 10.1126/science.2999973. [DOI] [PubMed] [Google Scholar]
- Nishikori M., Hansen H., Jhanwar S., Fried J., Sordillo P., Koziner B., Lloyd K., Clarkson B. Establishment of a near-tetraploid B-cell lymphoma line with duplication of the 8;14 translocation. Cancer Genet Cytogenet. 1984 May;12(1):39–50. doi: 10.1016/0165-4608(84)90006-2. [DOI] [PubMed] [Google Scholar]
- Papayannopoulou T., Brice M., Yokochi T., Rabinovitch P. S., Lindsley D., Stamatoyannopoulos G. Anti-HEL cell monoclonal antibodies recognize determinants that are also present in hemopoietic progenitors. Blood. 1984 Feb;63(2):326–334. [PubMed] [Google Scholar]
- Reed K. C., Mann D. A. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. doi: 10.1093/nar/13.20.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schneider U., Schwenk H. U., Bornkamm G. Characterization of EBV-genome negative "null" and "T" cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non-Hodgkin lymphoma. Int J Cancer. 1977 May 15;19(5):621–626. doi: 10.1002/ijc.2910190505. [DOI] [PubMed] [Google Scholar]
- Scott A. F., Phillips J. A., 3rd, Migeon B. R. DNA restriction endonuclease analysis for localization of human beta- and delta-globin genes on chromosome 11. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4563–4565. doi: 10.1073/pnas.76.9.4563. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shen S. H., Smithies O. Human globin psi B2 is not a globin-related sequence. Nucleic Acids Res. 1982 Dec 11;10(23):7809–7818. doi: 10.1093/nar/10.23.7809. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takegawa S., Brice M., Stamatoyannopoulos G., Papayannopoulou T. Only adult hemoglobin is produced in fetal nonerythroid x MEL cell hybrids. Blood. 1986 Dec;68(6):1384–1388. [PubMed] [Google Scholar]
- Taramelli R., Kioussis D., Vanin E., Bartram K., Groffen J., Hurst J., Grosveld F. G. Gamma delta beta-thalassaemias 1 and 2 are the result of a 100 kbp deletion in the human beta-globin cluster. Nucleic Acids Res. 1986 Sep 11;14(17):7017–7029. doi: 10.1093/nar/14.17.7017. [DOI] [PMC free article] [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]
- Tuan D., Solomon W., Li Q., London I. M. The "beta-like-globin" gene domain in human erythroid cells. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6384–6388. doi: 10.1073/pnas.82.19.6384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vanin E. F., Henthorn P. S., Kioussis D., Grosveld F., Smithies O. Unexpected relationships between four large deletions in the human beta-globin gene cluster. Cell. 1983 Dec;35(3 Pt 2):701–709. doi: 10.1016/0092-8674(83)90103-4. [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]
- 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]
- Wu C. The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 1980 Aug 28;286(5776):854–860. doi: 10.1038/286854a0. [DOI] [PubMed] [Google Scholar]