Crossref journal-article
Cold Spring Harbor Laboratory
Genome Research (246)
Abstract

The genetic stability of tandemly repeated DNAs is affected by repeat sequence, tract length, tract purity, and replication direction. Alterations in DNA methylation status are thought to influence many processes of mutagenesis. By use of bacterial and primate cell systems, we have determined the effect of CpG methylation on the genetic stability of cloned di-, tri-, penta- and minisatellite repeated DNA sequences. Depending on the repeat sequence, methylation can significantly enhance or reduce its genetic stability. This effect was evident when repeat tracts were replicated from either direction. Unexpectedly, methylation of adjacent sequences altered the stability of contiguous repeat sequences void of methylatable sites. Of the seven repeat sequences investigated, methylation stabilized five, destabilized one, and had no effect on another. Thus, although methylation generally stabilized repeat tracts, its influence depended on the sequence of the repeat. The current results lend support to the notion that the biological consequences of CpG methylation may be affected through local alterations of DNA structure as well as through direct protein–DNA interactions. In vivo CpG methylation in bacteria may have technical applications for the isolation and stable propagation of DNA sequences that have been recalcitrant to isolation and/or analyses because of their extreme instability.[Supplementary material available online athttp://www.genome.org.]

Bibliography

Nichol, K., & Pearson, and C. E. (2002). CpG Methylation Modifies the Genetic Stability of Cloned Repeat Sequences. Genome Research, 12(8), 1246–1256.

Authors 2
  1. Kerrie Nichol (first)
  2. and Christopher E. Pearson (additional)
References 66 Referenced 51
  1. 10.1002/(SICI)1096-8628(19960809)64:2<329::AID-AJMG19>3.0.CO;2-H
  2. 10.1093/hmg/2.9.1397
  3. 10.1016/S0092-8674(00)81532-9
  4. 10.1038/35057274
  5. 10.1006/jmbi.1996.0625
  6. 10.1093/hmg/8.6.1061
  7. 10.1089/10906570050501443
  8. 10.1016/S0021-9258(19)41284-2 / J. Biol. Chem. / Transmission of stability (telestability) in deoxyribonucleic acid. Physical and enzymatic studies on the duplex block polymer d(C15A15) - d(T15G15). by Burd (1975)
  9. 10.1093/hmg/8.12.2293
  10. 10.1002/j.1460-2075.1984.tb01959.x / Embo. J. / Assembly of transfected DNA into chromatin: Structural changes in the origin-promoter-enhancer region upon replication. by Cereghini (1984)
  11. 10.1038/25779
  12. 10.1038/8807
  13. 10.1093/hmg/9.6.909
  14. 10.1146/annurev.ge.29.120195.001553
  15. {'key': '2021111810471179000_12.8.1246.15', 'first-page': '4749', 'article-title': 'Diagnostic microsatellite instability: Definition and correlation with mismatch repair protein expression.', 'volume': '57', 'author': 'Dietmaier', 'year': '1997', 'journal-title': 'Cancer Res.'} / Cancer Res. / Diagnostic microsatellite instability: Definition and correlation with mismatch repair protein expression. by Dietmaier (1997)
  16. {'key': '2021111810471179000_12.8.1246.16', 'first-page': 'F79', 'article-title': 'A new concept in (adenoviral) oncogenesis: Integration of foreign DNA and its consequences.', 'volume': '1288', 'author': 'Doerfler', 'year': '1996', 'journal-title': 'Biochim. Biophys. Acta.'} / Biochim. Biophys. Acta. / A new concept in (adenoviral) oncogenesis: Integration of foreign DNA and its consequences. by Doerfler (1996)
  17. 10.1101/gr.188901
  18. 10.1126/science.279.5352.853
  19. 10.1073/pnas.86.19.7465
  20. 10.1093/nar/28.10.2141
  21. {'key': '2021111810471179000_12.8.1246.21', 'first-page': '73', 'article-title': 'Intriguing association between disease associated unstable trinucleotide repeat and CpG island.', 'volume': '40', 'author': 'Gourdon', 'year': '1997', 'journal-title': 'Ann. Genet.'} / Ann. Genet. / Intriguing association between disease associated unstable trinucleotide repeat and CpG island. by Gourdon (1997)
  22. 10.1073/pnas.80.21.6470
  23. 10.1016/0163-7258(94)00053-6
  24. {'key': '2021111810471179000_12.8.1246.24', 'first-page': '253', 'article-title': 'Monozygotic twin brothers with the fragile X syndrome: Different CGG repeats and different mental capacities.', 'volume': '36', 'author': 'Helderman-van den Enden', 'year': '1999', 'journal-title': 'J. Med. Genet.'} / J. Med. Genet. / Monozygotic twin brothers with the fragile X syndrome: Different CGG repeats and different mental capacities. by Helderman-van den Enden (1999)
  25. 10.1073/pnas.95.12.6870
  26. 10.1093/nar/26.10.2353
  27. 10.1021/bi00148a022
  28. 10.1002/j.1460-2075.1986.tb04437.x / Embo. J. / Molecular characterisation of a hypervariable region downstream of the human alpha-globin gene cluster. by Jarman (1986)
  29. 10.1093/hmg/2.6.731
  30. 10.1016/S0021-9258(18)41794-2 / J. Biol. Chem. / GC-rich flanking tracts decrease the kinetics of intramolecular DNA triplex formation. by Kang (1992)
  31. 10.1038/ng0695-213
  32. {'key': '2021111810471179000_12.8.1246.32', 'first-page': '2719', 'article-title': 'Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors.', 'volume': '53', 'author': 'Makos', 'year': '1993', 'journal-title': 'Cancer Res.'} / Cancer Res. / Regional DNA hypermethylation at D17S5 precedes 17p structural changes in the progression of renal tumors. by Makos (1993)
  33. 10.1038/ng0297-165
  34. 10.1093/hmg/6.6.877
  35. 10.1074/jbc.275.9.6447
  36. 10.1093/nar/14.19.7569
  37. 10.1086/302543
  38. 10.1074/jbc.M109761200
  39. 10.1021/bi9601013
  40. 10.1021/bi972546c
  41. 10.1016/S0021-9258(17)44902-7 / J. Biol. Chem. / Flanking AT-rich tracts cause a structural distortion in Z-DNA in plasmids. by Rajagopalan (1990)
  42. 10.1093/hmg/4.suppl_1.1751 / Hum. Mol. Genet. / DNA methylation in early development. by Razin (1995)
  43. 10.1093/nar/18.5.1145
  44. 10.1111/j.1469-1809.1996.tb00437.x / Ann. Hum. Genet. / Dynamic mutation loci: Allele distributions in different populations. by Richards (1996)
  45. 10.1073/pnas.85.19.7064
  46. 10.1136/jmg.37.11.842
  47. 10.1038/ng1197-298
  48. 10.1006/jmbi.1996.0273
  49. 10.1002/(SICI)1098-2744(199909)26:1<1::AID-MC1>3.0.CO;2-P
  50. 10.1086/301711
  51. 10.1016/0092-8674(86)90287-4
  52. 10.1016/0092-8674(86)90524-6
  53. 10.1038/35075692
  54. 10.1034/j.1399-0004.1999.550508.x
  55. 10.1002/(SICI)1096-8628(19990528)84:3<233::AID-AJMG14>3.0.CO;2-6
  56. 10.1073/pnas.96.15.8681
  57. 10.1089/10906570050501434
  58. 10.1126/science.3281259
  59. 10.1074/jbc.271.38.22937
  60. 10.1128/MCB.19.8.5675 / Mol. Cell Biol. / Stability of the human fragile X (CGG)(n) triplet repeat array in Saccharomyces cerevisiae deficient in aspects of DNA metabolism. by White (1999)
  61. 10.1093/hmg/4.7.1147
  62. 10.1136/jmg.35.2.103
  63. 10.1086/322739
  64. 10.1038/46052
  65. 10.1016/S0168-9525(97)01181-5
  66. {'key': '2021111810471179000_12.8.1246.66', 'first-page': '27', 'article-title': 'Methylation of cytosine influences the DNA structure.', 'volume': '64', 'author': 'Zacharias', 'year': '1993', 'journal-title': 'EXS.'} / EXS. / Methylation of cytosine influences the DNA structure. by Zacharias (1993)
Dates
Type When
Created 22 years, 9 months ago (Nov. 13, 2002, 2:12 p.m.)
Deposited 3 years, 9 months ago (Nov. 18, 2021, 2:13 p.m.)
Indexed 1 month, 3 weeks ago (July 4, 2025, 12:51 a.m.)
Issued 23 years, 1 month ago (July 19, 2002)
Published 23 years, 1 month ago (July 19, 2002)
Published Online 23 years, 1 month ago (July 19, 2002)
Published Print 23 years ago (Aug. 1, 2002)
Funders 0

None

@article{Nichol_2002, title={CpG Methylation Modifies the Genetic Stability of Cloned Repeat Sequences}, volume={12}, ISSN={1549-5469}, url={http://dx.doi.org/10.1101/gr.74502}, DOI={10.1101/gr.74502}, number={8}, journal={Genome Research}, publisher={Cold Spring Harbor Laboratory}, author={Nichol, Kerrie and Pearson, and Christopher E.}, year={2002}, month=jul, pages={1246–1256} }