Experimental Hematology
Volume 37, Issue 7 , Pages 807-813.e2 , July 2009

Developmentally regulated extended domains of DNA hypomethylation encompass highly transcribed genes of the human β-globin locus

  • Melissa J. Lathrop

      Affiliations

    • Departments of Microbiology/Immunology and Genetics, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH., USA
  • ,
  • Mei Hsu

      Affiliations

    • Departments of Microbiology/Immunology and Genetics, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH., USA
  • ,
  • Christine A. Richardson

      Affiliations

    • Departments of Medicine, and Pharmacology and Toxicology, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH., USA
  • ,
  • Emmanuel N. Olivier

      Affiliations

    • Einstein Center for Human Embryonic Stem Cell Research, Department of Medicine, Hematology and Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY., USA
  • ,
  • Caihong Qiu

      Affiliations

    • Einstein Center for Human Embryonic Stem Cell Research, Department of Medicine, Hematology and Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY., USA
  • ,
  • Eric E. Bouhassira

      Affiliations

    • Einstein Center for Human Embryonic Stem Cell Research, Department of Medicine, Hematology and Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY., USA
  • ,
  • Steven Fiering

      Affiliations

    • Departments of Microbiology/Immunology and Genetics, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH., USA
  • ,
  • Christopher H. Lowrey

      Affiliations

    • Departments of Medicine, and Pharmacology and Toxicology, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH., USA
    • Corresponding Author InformationOffprint requests to: Christopher H. Lowrey, M.D., Ph.D., Dartmouth Medical School, 1 Medical Center Drive, 622 Rubin Building, Lebanon, NH 03756

Received 23 January 2009 ,Revised 2 April 2009 ,Accepted 20 April 2009.

References 

  1. Stamatoyannopoulos G. Control of globin gene expression during development and erythroid differentiation. Exp Hematol. 2005;33:259–271
  2. Fathallah H, Atweh GF. Induction of fetal hemoglobin in the treatment of sickle cell disease. Hematology Am Soc Hematol Educ Program. 2006;58–62
  3. Fathallah H, Weinberg RS, Galperin Y, Sutton M, Atweh GF. Role of epigenetic modifications in normal globin gene regulation and butyrate-mediated induction of fetal hemoglobin. Blood. 2007;110:3391–3397
  4. Ginder GD, Gnanapragasam MN, Mian OY. The role of the epigenetic signal, DNA methylation, in gene regulation during erythroid development. Curr Topics Dev Biol. 2008;82:85–116
  5. van der Ploeg LH, Flavell RA. DNA methylation in the human gamma delta beta-globin locus in erythroid and nonerythroid tissues. Cell. 1980;19:947–958
  6. Ley TJ, Anagnou NP, Noguchi CT, et al. DNA methylation and globin gene expression in patients treated with 5-azacytidine. Prog Clin Biol Res. 1983;134:457–474
  7. Mavilio F, Giampaolo A, Care A, et al. Molecular mechanisms of human hemoglobin switching: selective undermethylation and expression of globin genes in embryonic, fetal, and adult erythroblasts. Proc Natl Acad Sci U S A. 1983;80:6907–6911
  8. Dover GJ, Charache SH, Boyer SH, Talbot CC, Smith KD. 5-Azacytidine increases fetal hemoglobin production in a patient with sickle cell disease. Prog Clin Biol Res. 1983;134:475–488
  9. Ley T, DeSimone J, Anagnou N, et al. 5-azacytidine selectively increases gamma-globin synthesis in a patient with β+thalassemia. N Engl J Med. 1982;301:1469–1475
  10. Lowrey C, Nienhius A. Brief report: treatment with azacytidine of patients with end-stage thalassemia. N Engl J Med. 1993;329:845–848
  11. Saunthararajah Y, Hillery CA, Lavelle D, et al. Effects of 5-aza-2'-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease. Blood. 2003;102:3865–3870
  12. Mabaera R, Richardson CA, Johnson K, Hsu M, Fiering S, Lowrey CH. Developmental- and differentiation-specific patterns of human gamma- and beta-globin promoter DNA methylation. Blood. 2007;110:1343–1352
  13. Mabaera R, Greene MR, Richardson CA, Conine SJ, Kozul CD, Lowrey CH. Neither DNA hypomethylation nor changes in the kinetics of erythroid differentiation explain 5-azacytidine's ability to induce human fetal hemoglobin. Blood. 2008;111:411–420
  14. Lavelle D, Chin J, Vaitkus K, et al. Oral decitabine reactivates expression of the methylated gamma-globin gene in Papio anubis. Am J Hematol. 2007;82:981–985
  15. Meissner A, Mikkelsen TS, Gu H, et al. Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature. 2008;454:766–770
  16. Saxonov S, Berg P, Brutlag DL. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A. 2006;103:1412–1417
  17. Takai D, Jones PA. Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A. 2002;99:3740–3745
  18. Weber M, Hellmann I, Stadler MB, et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. [see comment]. Nat Genet. 2007;39:457–466
  19. Bird A, Wolffe A. Methylation-induced repression- belts, braces and chromatin. Cell. 1999;99:451–454
  20. Boyes J, Bird A. Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl-CpG binding protein. EMBO J. 1992;11:327–333
  21. Klose R, Bird A. Genomic DNA methylation:the mark and its mediators. Trends Biochem Sci. 2006;31:89–97
  22. Ehrlich M, Jiang G, Fiala E, et al. Hypomethylation and hypermethylation of DNA in Wilms tumors. Oncogene. 2002;21:6694–6702
  23. Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002;3:415–428
  24. Kanai Y, Hirohashi S. Alterations of DNA methylation associated with abnormalities of DNA methyltransferases in human cancers during transition from a precancerous to a malignant state. Carcinogenesis. 2007;28:2434–2442
  25. Sato N, Maitra A, Fukushima N, et al. Frequent hypomethylation of multiple genes overexpressed in pancreatic ductal adenocarcinoma. Cancer Res. 2003;63:4158–4166
  26. Sato N, Fukushima N, Matsubayashi H, Goggins M. Identification of maspin and S100P as novel hypomethylation targets in pancreatic cancer using global gene expression profiling. Oncogene. 2004;23:1531–1538
  27. Ballestar E, Paz MF, Valle L, et al. Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer. EMBO J. 2003;22:6335–6345
  28. Weber M, Schubeler D. Genomic patterns of DNA methylation: targets and function of an epigenetic mark. Curr Opin Cell Biol. 2007;19:273–280
  29. Reiner SL. Epigenetic control in the immune response. Hum Mol Genet. 2005;14(spec no 1):R41–R46
  30. Shen HM, Nakamura A, Sugimoto J, et al. Tissue specificity of methylation and expression of human genes coding for neuropeptides and their receptors, and of a human endogenous retrovirus K family. J Hum Genet. 2006;51:440–450
  31. Yin W, Barkess G, Fang X, et al. Histone acetylation at the human beta-globin locus changes with developmental age. Blood. 2007;110:4101–4107
  32. Hsu M, Richardson CA, Olivier E, et al. Complex developmental patterns of histone modifications associated with the human β-globin switch in primary cells. Exp Hematol. 2009;37:799–806
  33. Hsu M, Mabaera R, Lowrey CH, Martin DI, Fiering S. CpG hypomethylation in a large domain encompassing the embryonic {beta}-like globin genes in primitive erythrocytes. Mol Cell Biol. 2007;27:5047–5054
  34. Qiu C, Olivier EN, Velho M, Bouhassira EE. Globin switches in yolk sac-like primitive and fetal-like definitive red blood cells produced from human embryonic stem cells. Blood. 2008;111:2400–2408
  35. Qiu C, Hanson E, Olivier E, et al. Differentiation of human embryonic stem cells into hematopoietic cells by coculture with human fetal liver cells recapitulates the globin switch that occurs early in development. Exp Hematol. 2005;33:1450–1458
  36. Rochette J, Craig JE, Thein SL. Fetal hemoglobin levels in adults. Blood Rev. 1994;8:213–224
  37. Boyer SH, Belding TK, Margolet L, Noyes AN. Fetal hemoglobin restriction to a few erythrocytes (F cells) in normal human adults. Science. 1975;188:361–363
  38. Wood W, Stamatoyannopolous G, Lim G, Nute P. F-cells in the adult: normal values and levels in individuals with hereditary and acquired elevations of HbF. Blood. 1975;46:671–682
  39. Gribnau J, Diderich K, Pruzina S, Calzolari R, Fraser P. Intergenic transcription and developmental remodeling of chromatin subdomains in the human beta-globin locus. Mol Cell. 2000;5:377–386
  40. Lee DU, Agarwal S, Rao A. Th2 lineage commitment and efficient IL-4 production involves extended demethylation of the IL-4 gene. Immunity. 2002;16:649–660
  41. Bulger M, Groudine M. Looping vs. linking: toward a model for long-distance gene activation. Genes Dev. 1999;13:2465–2477
  42. Papayannopoulou T, Shepard TH, Stamatoyannopoulos G. Studies of hemoglobin expression in erythroid cells of early human fetuses using anti-gamma- and anti-beta-globin chain fluorescent antibodies. Prog Clin Biol Res. 1983;134:421–430
  43. Stamatoyannopoulos G, Grosveld G. Red cells: hemoglobin switching. In:  Stamatoyannopoulos G,  Majerus PW,  Perlmutter RM,  Varmus H editor. The Molecular Basis of Blood Disease. 3rd ed. Philadelphia: WB Saunders Co; 2001;p. 135–182
  44. Jane SM, Gumucio DL, Ney PA, Cunningham JM, Nienhuis AW. Methylation-enhanced binding of Sp1 to the stage selector element of the human gamma-globin gene promoter may regulate development specificity of expression. Mol Cell Biol. 1993;13:3272–3281
  45. Sengupta PK, Lavelle D, DeSimone J. Increased binding of Sp1 to the gamma-globin gene promoter upon site-specific cytosine methylation. Am J Hematol. 1994;46:169–172
  46. Rupon JW, Wang SZ, Gaensler K, Lloyd J, Ginder GD. Methyl binding domain protein 2 mediates gamma-globin gene silencing in adult human betaYAC transgenic mice. Proc Natl Acad Sci U S A. 2006;103:6617–6622
  47. Singal R, Ferris R, Little J, Wang S, Ginder G. Methylation of the minimal promoter of an embryonic globin gene silences transcription in primary erythroid cells. Proc Natl Acad Sci U S A. 1997;94:13724–13729
  48. Singal R, Wang SZ, Sargent T, Zhu SZ, Ginder GD. Methylation of promoter proximal-transcribed sequences of an embryonic globin gene inhibits transcription in primary erythroid cells and promotes formation of a cell type-specific methyl cytosine binding complex. The J Biol Chem. 2002;277:1897–1905
  49. Brinkman AB, Pennings SW, Braliou GG, Rietveld LE, Stunnenberg HG. DNA methylation immediately adjacent to active histone marking does not silence transcription. Nucleic Acids Res. 2007;35:801–811
  50. Nute PE, Pataryas HA, Stamatoyannopoulos G. The G and A hemoglobin chains during human fetal development. Am J Hum Genet. 1973;25:271–276
  51. Lorincz MC, Dickerson DR, Schmitt M, Groudine M. Intragenic DNA methylation alters chromatin structure and elongation efficiency in mammalian cells. Nat Struct Mol Biol. 2004;11:1068–1075
  52. Goren A, Simchen G, Fibach E, et al. Fine tuning of globin gene expression by DNA methylation. PLoS ONE. 2006;1:e46

PII: S0301-472X(09)00133-7

doi: 10.1016/j.exphem.2009.04.005

Experimental Hematology
Volume 37, Issue 7 , Pages 807-813.e2 , July 2009