Skip to main content
SpringerLink
Log in
Book cover

DNA Methylation pp 385–403Cite as

DNA methylation: Its possible functional roles in developmental regulation of human globin gene families

  • Chapter

Part of the book series: EXS ((EXS,volume 64))

Abstract

The eukaryotic globin gene family is one of the first gene systems whose regulatory mechanisms of tissue-specific transcription appeared to involve DNA methylation of specific CpG residues (reviewed in Shen, 1984). In this chapter, we review the various experiments carried out since 1984 on the relationship between DNA methylation and transcriptional regulation of different human globin genes during erythroid development. We hope the article complements several earlier reviews on similar topics (Bird, 1984; Karlsson and Nienhuis, 1985; Cedar, 1989; Weissbach et al., 1989).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Antequera, F., Boyes, J., and Bird, A. (1990) High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell 62, 503–514.

    Article  PubMed  CAS  Google Scholar 

  • Anagnou, N. P., Karlsson, S., Moulton, A. D., Keller, G., and Nienhuis, A. W. (1986) Promoter sequences required for function of human y globin gene in erythroid cells. EMBO J. 5, 121–126.

    PubMed  CAS  Google Scholar 

  • Arapinis, C., Elion, J., Labie, D., and Krishnamoorthy, R. (1986) Differences in DNase I sensitivity and methylation within the human f$-globin gene domain and correlation with expression. Eur. J. Biochem. 156, 123–129.

    Article  PubMed  CAS  Google Scholar 

  • Becker, P. B., Ruppert, S., and Schutz, G. (1987) Genomic footprinting reveals cell type- specific DNA binding of ubiquitous factors. Cell 51, 435–443.

    Article  PubMed  CAS  Google Scholar 

  • Bird, A. P. (1984) DNA methylation - how important in gene control? Nature 307, 503–504.

    Article  PubMed  CAS  Google Scholar 

  • Bird, A. P. (1986) CpG-rich islands and the function of DNA methylation. Nature 321, 209–213.

    Article  PubMed  CAS  Google Scholar 

  • Bird, A. P., Taggart, M. H., Nicholls, R. D., and Higgs, D. R. (1987) Non-methylated CpG-rich islands at the human a-globin locus: implication for evolution of the a-globin pseudogene. EMBO J. 6, 999 - 1004.

    PubMed  CAS  Google Scholar 

  • Boyes, J., and Bird, A. (1991) DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell 64, 1123–1134.

    Article  PubMed  CAS  Google Scholar 

  • Boyes, J., and Bird, A. (1992) Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein. EMBO J. 11, 327–333.

    PubMed  CAS  Google Scholar 

  • Burns, L. J., Glauber, J. G., and Ginder, G. D. (1988) Butyrate induces selective transcriptional activation of a hypomethylated embryonic globin gene in adult erythroid cells. Blood 72, 1536–1542.

    PubMed  CAS  Google Scholar 

  • Busslinger, M., Hurst, J., and Flavell, R. A. (1983a) DNA methylation and regulation of globin gene expression. Cell 34, 197–206.

    Article  PubMed  CAS  Google Scholar 

  • Busslinger, M., and Flavell, R. A. (1983b) DNA methylation and the regulation of globin gene expression, in: Globin Gene Expression and Hematopoietic Differentiation, pp. 193–203. Eds G. Stamatoyannopoulos and A. Nienhuis. Alan R. Liss, New York.

    Google Scholar 

  • Catala, F., deBoer, E., Habets, G., and Grosveld, F. (1989) Nuclear protein factors and erythroid transcription of the human Ay globin gene. Nucleic Acids Res. 17, 3811–3827.

    Article  PubMed  CAS  Google Scholar 

  • Cedar, H. (1988) DNA methylation and gene activity. Cell 53, 3–4.

    Article  PubMed  CAS  Google Scholar 

  • Charache, S., Dover, G., Smith, K., Talbot, C. C., Moyer, M., and Boyer, S. (1983) Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with non-random hypomethylation of DNA around the y-S-p-globin gene complex. Proc. Natl. Acad. Sci. USA 80, 4842–4846.

    Article  PubMed  CAS  Google Scholar 

  • Charnay, P., Mellon, P., and Maniatis, T. (1985) Linker scanning mutagenesis of the 5’-flanking region of the mouse /?-major-globin gene: sequence requirements for transcription in erythroid and nonerythroid cells. Mol. Cell. Biol. 5, 1498–1511.

    PubMed  CAS  Google Scholar 

  • deBoer, E., Antoniou, M., Mignotte, V., Wall, L., and Grosveld, F. (1988) The human p globin promoter: Nuclear protein factors and erythroid specific induction of transcription. EMBO J. 7, 4203–4212.

    PubMed  CAS  Google Scholar 

  • DeSimone, J., Heller, P., Hall, L., and Zwiero, D. (1982) 5-Azacytidine stimulates fetal hemoglobin synthesis in anemic baboons. Proc. Natl. Acad. Sci. USA 79, 4428–4431.

    Google Scholar 

  • Elgin, S. C. R. (1988) The formation and function of DNase I hypersensitive sites in the process of gene inactivation. J. Biol. Chem. 263, 19259–19262.

    PubMed  CAS  Google Scholar 

  • Enver, T., Zhang, J.-W., Anagnou, N. P., Stamatoyannopoulos, G., and Papyannopoulou, T. (1988a) Developmental programs of human erythroleukemia cells: globin gene expression and methylation. Mol. Cell. Biol. 8, 4917–4926.

    PubMed  CAS  Google Scholar 

  • Enver, T., Zhang, J.-W., Papyannopoulou, T., and Stamatoyannopoulos, G. (1988b) DNA methylation: a secondary event in globin gene switching? Genes Dev. 2, 698–706.

    Article  PubMed  CAS  Google Scholar 

  • Evans, T., Felsenfeld, G., and Reitman, M. (1990) Control of globin gene transcription. Annu. Rev. Cell Biol. 6, 95 - 124.

    Article  PubMed  CAS  Google Scholar 

  • Forrester, W. C., Thompson, C., Elder, J. T., and Groudine, M. (1986) A developmentally stable chromatin structure in the human p-globin gene cluster. Proc. Nat. Acad. Sci. USA 83, 1359–1363.

    Article  PubMed  CAS  Google Scholar 

  • Forrester, W. C., Takewaga, S., Papayannopoulou, T., Stamatoyannopoulos, G., and Groudine, M. (1987) Evidence for a locus activation region: The formation of developmentally stable hypersensitive sites in Gong, R. H., Stern, J., and Dean, A. (1991) Transcriptional role of a conserved GATA-1 site in the human g-globin gene promoter. Mol. Cell. Biol. 17, 2558–2566.

    Google Scholar 

  • Gong, R.H., Stern, J., and Dean, A. (1991) Transcriptional role of a conserved GAT-1 site in the human ɛ-globin gene promoter. Mol. Cell. Biol. 17, 2558–2566.

    Google Scholar 

  • Gross, D. S., and Garrard, W. T. (1988) Nuclease hypersensitive sites in chromatin. Annu. Rev. Biochem. 57, 159–197.

    Article  PubMed  CAS  Google Scholar 

  • Grosveld, F., Blom van Assendelft, G., Greaves, D. R., and Kollias, G. (1987) Position- independent high level expression of the human globin gene in transgenic mice. Cell 51, 975–985.

    Article  PubMed  CAS  Google Scholar 

  • Groudine, M., Kohwi-Shigematsu, T., Gelinas, R., Stamatoyannopoulos, G., and Pa- payannopoulou, T. (1983) Human fetal to adult hemoglobin switching: changes in chro-matin structure of the jS-globin gene locus. Proc. Natl. Acad. Sci. USA 80, 7551–7555.

    Article  PubMed  CAS  Google Scholar 

  • Gumucio, D. L., Rood, K. L., Gray, T. A., Riordan, M. F., Sartor, C. I., and Collins, F. S. (1988) Nuclear proteins that bind the human y-globin gene promoter: Alterations in binding produced by point mutations associated with hereditary persistence of fetal hemoglobin. Mol. Cell. Biol. 8, 5310–5322.

    PubMed  CAS  Google Scholar 

  • Harrington, M. A., Jones, P. A., Imagawa, M., and Karin, M. (1988) Cytosine methylation does not affect binding of transcription factor Spl. Proc. Natl. Acad. Sci. USA 85., 2066–2070.

    Google Scholar 

  • Higgs, D. R., Wood, W. G., Jarman, A. P., Sharpe, J., Lida, J., Pretorius, I.-M., and Ayyub, H. (1990) A major positive regulatory region located far upstream of the human a-globin gene locus. Genes Dev. 4, 1588–1601.

    Article  PubMed  CAS  Google Scholar 

  • Hsiao, W.-L. W., Gattoni-Celli, S., Kirschmeier, P., and Weinstein, I. B. (1984) Effect of 5-azacytidine on methylation and expression of specific DNA sequences in C3H 10T 1/2 cells. Mol. Cell. Biol. 4, 634–641.

    PubMed  CAS  Google Scholar 

  • Iguchi-Ariga, S., and Schaffner, W. (1989) CpG methylation of the cAMP-responsive en-hancer/promoter sequence TGACGTCA abolishes specific factor binding as well as tran-scriptional activation. Genes Dev. 3, 612–619.

    Article  PubMed  CAS  Google Scholar 

  • Jones, P. A. (1984) Gene activation by 5-azacytidine, in: DNA Methylation: Biochemistry and Biological Significance, pp. 165-187. Eds A. Razin, H. Cedar and A. Riggs. Springer-Ver- lag, New York.

    Google Scholar 

  • Karlsson, S., and Nienhuis A. (1985) Developmental regulation of human globin genes. Annu. Rev. Biochem. 54, 1071–1108.

    Article  PubMed  CAS  Google Scholar 

  • Keshet, I., Lieman-Hurwitz, J., and Cedar, H. (1986) DNA methylation affects the formation of active chromatin. Cell 44, 535–543.

    Article  PubMed  CAS  Google Scholar 

  • Khan, R., Zhang, X.-Y., Supakar, P. C., Ehrlich, K. C., and Ehrlich, M. (1988) Human methylated DNA-binding protein: determinants of a pBR322 recognition site. J. Biol. Chem. 263, 14,374–14, 383.

    Google Scholar 

  • Letvin, N. L., Linch, D. C., Beardsley, G. P., Mclntyre, K. W., and Nathan, D. G. (1984) Augmentation of fetal-hemoglobin production in anemic monkeys by hydroxyurea. N. Engl. J. Med. 310, 869–873.

    Article  PubMed  CAS  Google Scholar 

  • Ley, T. J., DeSimone, J., Anagnou, N. P., Keller, G., Humphries, R. K., Turner, P. H., Young, N. S., Heller, P., and Nienhuis, A. W. (1982) 5-Azacytidine selectively increases y-globin synthesis in a patient with ft + -thalassemia. N. Engl. J. Med. 307, 1469–1475.

    Google Scholar 

  • Ley, T. J., DeSimone, J., Noguchi, C. T., Turner, P. H., Schechter, A. N., Heller, P., and Nienhuis, A. W. (1983) 5-Azacytidine increases y-globin synthesis and reduces the propor¬tion of dense cells in patients with sickle cell anemia. Blood 62, 370–380.

    Google Scholar 

  • Ley, T. J., Chiang, Y. L., Haidaris, D., Anagnou, N. P., Wilson, V. L., and Anderson, W. F. (1984) DNA methylation and regulation of the human ?-globin-like genes in mouse erythroluekemia cells containing human chromosome 11. Proc. Natl. Acad. Sci. USA 81, 6618–6622.

    Article  PubMed  CAS  Google Scholar 

  • Lloyd, J. A., Lee, R. F., and Lingrel, J. B. (1989) Mutations in two regions of the Ay globin canonical promoter affect gene expression. Nucl. Acids Res. 17, 4339–4352.

    Article  PubMed  CAS  Google Scholar 

  • Martin, D. I. K., Tsai, S. F., and Orkin, S. H. (1989) Increased y-globin expression in a non-deletion HPFH mediated by an erythroid-specific DNA-binding factor. Nature 388, 435–438.

    Article  Google Scholar 

  • Mavilio, F., Giampaolo, A., Care, A., Migliaccio, G., Calandrini, M., Russo, G., Pagliardi, G. L., Mastroberardino, G., Marinucci, M., and Peschle, C. (1983) Molecular mechanisms of human hemoglobin switching: selective under-methylation and expression of globin genes in embryonic, fetal and adult erythroblasts. Proc. Natl. Acad. Sci. USA 80, 6907–6911.

    Article  PubMed  CAS  Google Scholar 

  • McGhee, J. D., Wood, W. I., Dolan, J., Engel, J. D., and Felsenfeld, G. (1981) A 200 base pair region at the 5’ end of the chicken adult β-globin gene is accessible to nuclease digestion. Cell 27, 45–55.

    Article  PubMed  CAS  Google Scholar 

  • Meehan, R. R., Lewis, J. D., McKay, S., Kleiner, E. L., and Bird, A. P. (1989) Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell 58, 499–507.

    Article  PubMed  CAS  Google Scholar 

  • Michalowsky, L. A., and Jones, P. A. (1989) Gene structure and transcription in mouse cells with extensively demethylated DNA. Mol. Cell. Biol. 9, 885–892.

    PubMed  CAS  Google Scholar 

  • Murray, E. J., and Grosveld, F. (1987) Site specific demethylation in the promoter of human y-globin gene does not alleviate methylation mediated suppression. EMBO J. 6, 2329— 2335.

    PubMed  CAS  Google Scholar 

  • Nicolis, S., Ronchi, A., Malgarette, N., Mantovani, R., Giglioni, B., and Ottolenghi, S. (1989) Increased erythroid-specific expression of a mutated HPFH y-globin promoter requires the erythroid factor NF-E1. Nucl. Acids Res. 17, 5509–5516.

    Article  PubMed  CAS  Google Scholar 

  • Oppenheim, A., Katzir, Y., Fibach, E., Goldfarb, A., and Rachmilewitz, E. (1985) Hy- pomethylation of DNA derived from purified human erythroid cells correlates with gene activity of the j?-globin cluster. Blood 66, 1202–1207.

    PubMed  CAS  Google Scholar 

  • Orkin, S. H. (1990) Globin gene regulation and switching: circa 1990. Cell 63, 665–672.

    Article  PubMed  CAS  Google Scholar 

  • Papayannopoulou, T., Torrealba-de ron, A., Veith, R., Knitter, G., and Stamatoyannopoulos, G. (1984) Arabinosylcytosine induces fetal hemoglobin in baboons by perturbing cell differentiation kinetics. Science 224, 617–618.

    Article  PubMed  CAS  Google Scholar 

  • Paroush, A., Keshet, I., Yisraeli, J., and Cedar, H. (1990) Dynamics of demethylation and activation of the a-actin gene in myoblasts. Cell 63, 1229–1237.

    Article  PubMed  CAS  Google Scholar 

  • Perrine, S. P., Greene, M. F., Cohen, R. A., and Faller, D. V. (1988) A physiological delay in human fetal hemoglobin switching is associated with specific globin DNA hypomethyla- tion. FEBS Lett. 228, 139–143.

    Article  PubMed  CAS  Google Scholar 

  • Peschle, C., Mavilio, F., Care, A., Migliaccio, G., Migliaccio, A. R., Salvo, G., Samoggia, P., Petli, S., Guerriero, R., Marinucci, M., Lazzaro, D., Russo, G., and Mastroberadino, G. (1985) Haemoglobin switching in human embryos: Asynchrony of £ to a and e to y globin switches in primitive and definitive erythropoietic lineages. Nature 313, 235–238.

    Article  PubMed  CAS  Google Scholar 

  • Razin, A., Levine, A., Kafri, T., Agostini, S., Gomi, T., and Cantoni, G. L. (1988) Relationship between transient DNA hypomethylation and erythroid differentiation of murine erythroleukemia cells. Proc. Natl. Acad. Sci. USA 85, 9003–9006.

    Article  PubMed  CAS  Google Scholar 

  • Shen, C.-K. J. (1984) DNA methylation and developmental regulation of eukaryotic globin gene transcription, in: DNA methylation: Biochemistry and Biological Significance, pp. 249–268. Eds A. Razin, H. Cedar, and A. D. Riggs. Springer-Verlag, New York.

    Google Scholar 

  • Shen, C.-K. J., and Maniatis, T. (1980) Tissue-specific DNA methylation in a cluster of rabbit /Mike globin genes. Proc. Natl. Acad. Sci. USA 77, 6634–6638.

    Article  PubMed  CAS  Google Scholar 

  • Shen, C.-C., Bailey, A. D., Kim, S. H., Yu, C.-Y., Marks, J., Shaw, J.-P., Klisak, I., Sparkes, R. and Shen, C.-K. J. (1989) The human a2-al-01 globin locus: some thoughts and recent studies of its evolution and regulation, in: Hemoglobin Switching, pp. 19–32. Eds G. Stamatoyannopoulos and A. Nienhuis. Alan R. Liss, New York.

    Google Scholar 

  • Stamatoyannopoulos, G. (1991) Human hemoglobin switching. Science 252, 383.

    Article  PubMed  CAS  Google Scholar 

  • Stein, R., Gruenbaum, Y., Pollack, Y., Razin, A., and Cedar, H. (1982) Clonal inheritance of the pattern of DNA methylation in mouse cells. Proc. Natl. Acad. Sci. USA 79, 61–65.

    Article  PubMed  CAS  Google Scholar 

  • Superti-Furga, G., Barberis, A., Schaffner, G., and Busslinger, M. (1988) The —117 mutation in Greek HPFH affects the binding of three nuclear factors to the CCAAT region of the y-globin gene. EMBO J. 7, 3099 - 3107.

    PubMed  CAS  Google Scholar 

  • Tuan, D., Solomon, D. W., Qiliang, L., and London, I. M. (1985) The “β Mike globin” gene domain in human erythroid cells. Proc. Natl. Acad. Sci. USA 82, 6384–6388.

    Article  PubMed  CAS  Google Scholar 

  • Tuan, D., Solomon, W., London, I. M., and Lee, D. P. (1989) An erythroid-specific, developmental-stage independent enhancer far upstream of human “βMike globin” genes. Proc. Natl. Acad. Sci. USA 86, 2554–2558.

    Article  PubMed  CAS  Google Scholar 

  • Van der Ploeg, L. H. T., and Flavell, R. A. (1980) DNA methylation in human y-d-jS-globin locus in erythroid and non-erythroid tissues. Cell 19, 947–958.

    Article  PubMed  Google Scholar 

  • Ward, C., Bolden, A., and Weissbach, A. (1990) Genomic sequencing of the 5’-flanking region of the mouse ft-globin major gene in expressing and nonexpressing mouse cells. J. Biol. Chem. 265, 3030–3033.

    PubMed  CAS  Google Scholar 

  • Watt, F., and Molloy, P. L. (1988) Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev. 2, 1136–1143.

    Article  PubMed  CAS  Google Scholar 

  • Weintraub, H., and Groudine, M. (1976) Chromosomal subunits in active genes have an altered conformation. Science 93, 848–858.

    Article  Google Scholar 

  • Weissbach, A., Ward, C., and Bolden, A. (1989) Eukaryotic DNA methylation and gene expression. Curr. Top. Cell. Reg. 30, 1–21.

    CAS  Google Scholar 

  • Whitelaw, E., Hogben, P., Hanscombe, O., and Proudfoot, N. J. (1989) Transcriptional promiscuity of the human a-globin gene. Mol. Cell. Biol. 9, 241–251.

    PubMed  CAS  Google Scholar 

  • Wright, S., Rosenthal, A., Flavell, R., and Grosveld, F. (1984) DNA sequences required for regulated expression of p-globin genes in murine erythroleukemia cells. Cell 38, 265–273.

    Article  PubMed  CAS  Google Scholar 

  • Wu, C., Bingham., P. M., Livak, K. J., Holmgren, R., and Elgin, S. C. R. (1979) The chromatin structure of specific genes: I. evidence for higher order domains of defined DNA sequences. Cell 16, 797–806.

    Article  PubMed  CAS  Google Scholar 

  • Yagi, M., Gelinas, R., Elder, J. T., Peretz, M., Papayannopoulou, T., Stamatoyannopoulos, G., and Groudine, M. (1986) Chromatin structure and developmental expression of the human a-globin cluster. Mol. Cell. Biol. 6, 1108–1116.

    PubMed  CAS  Google Scholar 

  • Yisraeli, J., Frank, D., Razin, A., and Cedar, H. (1988) Effect of in vitro DNA methylation on p-globin gene expression. Proc. Natl. Acad. Sci. USA 85, 4638–4642.

    Article  PubMed  CAS  Google Scholar 

  • Yu, C.-Y., Chen, J., Lin, L. I., Tam, M., and Shen, C.-K. J. (1990) Cell type-specific protein-DNA interaction in the human £-globin upstream promoter region: Displacement of Spl by the erythroid cell-specific factor NF-E1. Mol. Cell. Biol. 10, 282–294.

    PubMed  CAS  Google Scholar 

  • Yu, C.-Y., Motamed, K., Chen, J., Bailey, A. D., and Shen, C.-K. J. (1991) The CACC box upstream of human embryonic e globin gene binds Spl and is a functional promoter element in vivo and in vitro. J. Biol. Chem. 266, 8907–8915.

    PubMed  CAS  Google Scholar 

  • Zhu, J.-D., Allan, M., and Paul J. (1984) The chromatin structure of the human e globin gene: Nuclease hypersensitive sites correlate with multiple initiation sites of transcription. Nucl. Acids Res. 12, 9191–9204.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Genetics, University of California, Davis, CA, 95616, USA

    Chien Chu & C.-K. James Shen

Authors
  1. Chien Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C.-K. James Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Friedrich Miescher-Institut, P.O. Box 2543, CH-4002, Basel, Switzerland

    Jean-Pierre Jost

  2. IRBM, Via Pontina Km 30,600, I-00040, Pomenzia (Roma), Italy

    Hans-Peter Saluz

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Chu, C., Shen, CK.J. (1993). DNA methylation: Its possible functional roles in developmental regulation of human globin gene families. In: Jost, JP., Saluz, HP. (eds) DNA Methylation. EXS, vol 64. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-9118-9_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-9118-9_17

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-9915-4

  • Online ISBN: 978-3-0348-9118-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation