Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1988 Nov;7(11):3337–3344. doi: 10.1002/j.1460-2075.1988.tb03205.x

Nuclear scaffold attachment sites in the human globin gene complexes.

A P Jarman 1, D R Higgs 1
PMCID: PMC454829  PMID: 3208739

Abstract

In an analysis of a 90-kb region around the human beta-globin gene complex we have identified at least eight sites of attachment to the nuclear scaffold (SARs). While these have many potential functions, there appears to be a particular association with sequences important in the regulation of the complex. Two SARs are close to the known enhancer-like elements of the beta-globin gene. SARs flanking the complex co-habit with the boundaries of the putative beta-like globin gene regulatory domain. In contrast, we have detected no SARs within a 140-kb region of the human alpha-globin gene complex. If SARs play a role in the regulation of gene expression then this structural difference would imply a difference in the regulation of the two complexes.

Full text

PDF
3337

Images in this article

Selected References

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

  1. Antonarakis S. E., Boehm C. D., Giardina P. J., Kazazian H. H., Jr Nonrandom association of polymorphic restriction sites in the beta-globin gene cluster. Proc Natl Acad Sci U S A. 1982 Jan;79(1):137–141. doi: 10.1073/pnas.79.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. Benyajati C., Worcel A. Isolation, characterization, and structure of the folded interphase genome of Drosophila melanogaster. Cell. 1976 Nov;9(3):393–407. doi: 10.1016/0092-8674(76)90084-2. [DOI] [PubMed] [Google Scholar]
  5. Berezney R., Coffey D. S. Identification of a nuclear protein matrix. Biochem Biophys Res Commun. 1974 Oct 23;60(4):1410–1417. doi: 10.1016/0006-291x(74)90355-6. [DOI] [PubMed] [Google Scholar]
  6. Bernardi G., Olofsson B., Filipski J., Zerial M., Salinas J., Cuny G., Meunier-Rotival M., Rodier F. The mosaic genome of warm-blooded vertebrates. Science. 1985 May 24;228(4702):953–958. doi: 10.1126/science.4001930. [DOI] [PubMed] [Google Scholar]
  7. Berrios M., Osheroff N., Fisher P. A. In situ localization of DNA topoisomerase II, a major polypeptide component of the Drosophila nuclear matrix fraction. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4142–4146. doi: 10.1073/pnas.82.12.4142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bird A. P., Taggart M. H., Nicholls R. D., Higgs D. R. Non-methylated CpG-rich islands at the human alpha-globin locus: implications for evolution of the alpha-globin pseudogene. EMBO J. 1987 Apr;6(4):999–1004. doi: 10.1002/j.1460-2075.1987.tb04851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Cockerill P. N., Garrard W. T. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites. Cell. 1986 Jan 31;44(2):273–282. doi: 10.1016/0092-8674(86)90761-0. [DOI] [PubMed] [Google Scholar]
  11. Collins F. S., Cole J. L., Lockwood W. K., Iannuzzi M. C. The deletion in both common types of hereditary persistence of fetal hemoglobin is approximately 105 kilobases. Blood. 1987 Dec;70(6):1797–1803. [PubMed] [Google Scholar]
  12. Cook P. R., Brazell I. A. Supercoils in human DNA. J Cell Sci. 1975 Nov;19(2):261–279. doi: 10.1242/jcs.19.2.261. [DOI] [PubMed] [Google Scholar]
  13. Earnshaw W. C., Halligan B., Cooke C. A., Heck M. M., Liu L. F. Topoisomerase II is a structural component of mitotic chromosome scaffolds. J Cell Biol. 1985 May;100(5):1706–1715. doi: 10.1083/jcb.100.5.1706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fischel-Ghodsian N., Nicholls R. D., Higgs D. R. Long range genome structure around the human alpha-globin complex analysed by PFGE. Nucleic Acids Res. 1987 Aug 11;15(15):6197–6207. doi: 10.1093/nar/15.15.6197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fischel-Ghodsian N., Nicholls R. D., Higgs D. R. Unusual features of CpG-rich (HTF) islands in the human alpha globin complex: association with non-functional pseudogenes and presence within the 3' portion of the zeta gene. Nucleic Acids Res. 1987 Nov 25;15(22):9215–9225. doi: 10.1093/nar/15.22.9215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gasser S. M., Laemmli U. K. Cohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated genes of D. melanogaster. Cell. 1986 Aug 15;46(4):521–530. doi: 10.1016/0092-8674(86)90877-9. [DOI] [PubMed] [Google Scholar]
  17. Gasser S. M., Laemmli U. K. The organisation of chromatin loops: characterization of a scaffold attachment site. EMBO J. 1986 Mar;5(3):511–518. doi: 10.1002/j.1460-2075.1986.tb04240.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Grosveld F., van Assendelft G. B., Greaves D. R., Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. doi: 10.1016/0092-8674(87)90584-8. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Holmquist G. P. Role of replication time in the control of tissue-specific gene expression. Am J Hum Genet. 1987 Feb;40(2):151–173. [PMC free article] [PubMed] [Google Scholar]
  21. Igó-Kemenes T., Zachau H. G. Domains in chromatin structure. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 1):109–118. doi: 10.1101/sqb.1978.042.01.012. [DOI] [PubMed] [Google Scholar]
  22. Jackson D. A., Cook P. R. Replication occurs at a nucleoskeleton. EMBO J. 1986 Jun;5(6):1403–1410. doi: 10.1002/j.1460-2075.1986.tb04374.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. Käs E., Chasin L. A. Anchorage of the Chinese hamster dihydrofolate reductase gene to the nuclear scaffold occurs in an intragenic region. J Mol Biol. 1987 Dec 20;198(4):677–692. doi: 10.1016/0022-2836(87)90209-9. [DOI] [PubMed] [Google Scholar]
  26. Lebkowski J. S., Laemmli U. K. Non-histone proteins and long-range organization of HeLa interphase DNA. J Mol Biol. 1982 Apr 5;156(2):325–344. doi: 10.1016/0022-2836(82)90332-1. [DOI] [PubMed] [Google Scholar]
  27. Lewis C. D., Laemmli U. K. Higher order metaphase chromosome structure: evidence for metalloprotein interactions. Cell. 1982 May;29(1):171–181. doi: 10.1016/0092-8674(82)90101-5. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Loc P. V., Strätling W. H. The matrix attachment regions of the chicken lysozyme gene co-map with the boundaries of the chromatin domain. EMBO J. 1988 Mar;7(3):655–664. doi: 10.1002/j.1460-2075.1988.tb02860.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mirkovitch J., Mirault M. E., Laemmli U. K. Organization of the higher-order chromatin loop: specific DNA attachment sites on nuclear scaffold. Cell. 1984 Nov;39(1):223–232. doi: 10.1016/0092-8674(84)90208-3. [DOI] [PubMed] [Google Scholar]
  31. Nicholls R. D., Fischel-Ghodsian N., Higgs D. R. Recombination at the human alpha-globin gene cluster: sequence features and topological constraints. Cell. 1987 May 8;49(3):369–378. doi: 10.1016/0092-8674(87)90289-3. [DOI] [PubMed] [Google Scholar]
  32. Razin S. V. DNA interactions with the nuclear matrix and spatial organization of replication and transcription. Bioessays. 1987 Jan;6(1):19–23. doi: 10.1002/bies.950060106. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. 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]
  36. 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]
  37. 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]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES