Skip to main content
NCBI 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
. 1987 Nov;84(22):8105–8109. doi: 10.1073/pnas.84.22.8105

A chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch.

M Melis 1, G Demopulos 1, V Najfeld 1, J W Zhang 1, M Brice 1, T Papayannopoulou 1, G Stamatoyannopoulos 1
PMCID: PMC299487  PMID: 3479779

Abstract

Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control gamma-to-beta switching, we analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome-i.e., chromosome 11--sufficient for expression of human fetal globin and the subsequent gamma-to-beta switch. The results suggest that the gamma-to-beta switch is controlled either cis to the beta-globin locus or by a trans-acting mechanism, the genes of which reside on human chromosome 11.

Full text

PDF
8105

Images in this article

8106Image
on p.8106
8106Image
on p.8106

Selected References

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

  1. Barker D., Schafer M., White R. Restriction sites containing CpG show a higher frequency of polymorphism in human DNA. Cell. 1984 Jan;36(1):131–138. doi: 10.1016/0092-8674(84)90081-3. [DOI] [PubMed] [Google Scholar]
  2. Baron M. H., Maniatis T. Rapid reprogramming of globin gene expression in transient heterokaryons. Cell. 1986 Aug 15;46(4):591–602. doi: 10.1016/0092-8674(86)90885-8. [DOI] [PubMed] [Google Scholar]
  3. Beaudet A. L. Bibliography of cloned human and other selected DNAs. Am J Hum Genet. 1985 Mar;37(2):386–406. [PMC free article] [PubMed] [Google Scholar]
  4. Cavenee W., Leach R., Mohandas T., Pearson P., White R. Isolation and regional localization of DNA segments revealing polymorphic loci from human chromosome 13. Am J Hum Genet. 1984 Jan;36(1):10–24. [PMC free article] [PubMed] [Google Scholar]
  5. Chada K., Magram J., Costantini F. An embryonic pattern of expression of a human fetal globin gene in transgenic mice. Nature. 1986 Feb 20;319(6055):685–689. doi: 10.1038/319685a0. [DOI] [PubMed] [Google Scholar]
  6. Chu M. L., Myers J. C., Bernard M. P., Ding J. F., Ramirez F. Cloning and characterization of five overlapping cDNAs specific for the human pro alpha 1(I) collagen chain. Nucleic Acids Res. 1982 Oct 11;10(19):5925–5934. doi: 10.1093/nar/10.19.5925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deisseroth A., Hendrick D. Human alpha-globin gene expression following chromosomal dependent gene transfer into mouse erythroleukemia cells. Cell. 1978 Sep;15(1):55–63. doi: 10.1016/0092-8674(78)90082-x. [DOI] [PubMed] [Google Scholar]
  8. Deisseroth A., Nienhuis A., Lawrence J., Giles R., Turner P., Ruddle F. H. Chromosomal localization of human beta globin gene on human chromosome 11 in somatic cell hybrids. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1456–1460. doi: 10.1073/pnas.75.3.1456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gitschier J., Drayna D., Tuddenham E. G., White R. L., Lawn R. M. Genetic mapping and diagnosis of haemophilia A achieved through a BclI polymorphism in the factor VIII gene. 1985 Apr 25-May 1Nature. 314(6013):738–740. doi: 10.1038/314738a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Heisterkamp N., Groffen J., Stephenson J. R., Spurr N. K., Goodfellow P. N., Solomon E., Carritt B., Bodmer W. F. Chromosomal localization of human cellular homologues of two viral oncogenes. Nature. 1982 Oct 21;299(5885):747–749. doi: 10.1038/299747a0. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Leonard W. J., Donlon T. A., Lebo R. V., Greene W. C. Localization of the gene encoding the human interleukin-2 receptor on chromosome 10. Science. 1985 Jun 28;228(4707):1547–1549. doi: 10.1126/science.3925551. [DOI] [PubMed] [Google Scholar]
  14. Magram J., Chada K., Costantini F. Developmental regulation of a cloned adult beta-globin gene in transgenic mice. Nature. 1985 May 23;315(6017):338–340. doi: 10.1038/315338a0. [DOI] [PubMed] [Google Scholar]
  15. Matthyssens G., Rabbitts T. H. Structure and multiplicity of genes for the human immunoglobulin heavy chain variable region. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6561–6565. doi: 10.1073/pnas.77.11.6561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Najfeld V., Fialkow P. J., Karande A., Nilsson K., Klein G., Penfold G. Chromosome analyses of lymphoid cell lines derived from patients with chronic lymphocytic leukemia. Int J Cancer. 1980 Nov 15;26(5):543–549. doi: 10.1002/ijc.2910260504. [DOI] [PubMed] [Google Scholar]
  17. Papayannopoulou T. H., Lindsley D., Kurachi S., Lewison K., Hemenway T., Melis M., Anagnou N. P., Najfeld V. Adult and fetal human globin genes are expressed following chromosomal transfer into MEL cells. Proc Natl Acad Sci U S A. 1985 Feb;82(3):780–784. doi: 10.1073/pnas.82.3.780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Papayannopoulou T., Brice M., Stamatoyannopoulos G. Analysis of human hemoglobin switching in MEL x human fetal erythroid cell hybrids. Cell. 1986 Aug 1;46(3):469–476. doi: 10.1016/0092-8674(86)90667-7. [DOI] [PubMed] [Google Scholar]
  19. Proudfoot N. J., Gil A., Maniatis T. The structure of the human zeta-globin gene and a closely linked, nearly identical pseudogene. Cell. 1982 Dec;31(3 Pt 2):553–563. doi: 10.1016/0092-8674(82)90311-7. [DOI] [PubMed] [Google Scholar]
  20. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  21. Stewart G. D., Harris P., Galt J., Ferguson-Smith M. A. Cloned DNA probes regionally mapped to human chromosome 21 and their use in determining the origin of nondisjunction. Nucleic Acids Res. 1985 Jun 11;13(11):4125–4132. doi: 10.1093/nar/13.11.4125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Su T. S., Nussbaum R. L., Airhart S., Ledbetter D. H., Mohandas T., O'Brien W. E., Beaudet A. L. Human chromosomal assignments for 14 argininosuccinate synthetase pseudogenes: cloned DNAs as reagents for cytogenetic analysis. Am J Hum Genet. 1984 Sep;36(5):954–964. [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Tsipouras P., Myers J. C., Ramirez F., Prockop D. J. Restriction fragment length polymorphism associated with the pro alpha 2(I) gene of human type I procollagen. Application to a family with an autosomal dominant form of osteogenesis imperfecta. J Clin Invest. 1983 Oct;72(4):1262–1267. doi: 10.1172/JCI111082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Willing M. C., Nienhuis A. W., Anderson W. F. Selective activation of human beta-but not gamma-globin gene in human fibroblast x mouse erythroleukaemia cell hybrids. Nature. 1979 Feb 15;277(5697):534–538. doi: 10.1038/277534a0. [DOI] [PubMed] [Google Scholar]
  28. Wilson J. T., Wilson L. B., deRiel J. K., Villa-komaroff L., Efstratiadis A., Forget B. G., Weissman S. M. Insertion of synthetic copies of human globin genes into bacterial plasmids. Nucleic Acids Res. 1978 Feb;5(2):563–581. doi: 10.1093/nar/5.2.563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yagi M., Stamatoyannopoulos G., Papayannopoulou T. Monoclonal antibody 53.6 recognizes a novel proliferation-associated antigen encoded on human chromosome 11. J Immunol. 1987 Apr 1;138(7):2208–2212. [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