Methylation of discrete regions of the O6-methylguanine DNA methyltransferase (MGMT) CpG island is associated with heterochromatinization of the MGMT transcription start site and silencing of the gene

Molecular and Cellular Biology

Volumn 17, Issue 9, 1997, Pages 5612-5619

  Watts, George S ^a,b   Pieper, Russell O ^c   Costello, Joseph F ^d   Peng, Yei Mei ^b   Dalton, William S ^e   Futscher, Bernard W ^a,b,f  

^a UNIVERSITY OF ARIZONA   (United States)

^b UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

^c LOYOLA UNIVERSITY CHICAGO   (United States)

^d LUDWIG INSTITUTE FOR CANCER RESEARCH   (United States)

^e H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^f UNIVERSITY OF ARIZONA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 O METHYLGUANINE; METHYLATED DNA PROTEIN CYSTEINE METHYLTRANSFERASE;

ARTICLE; CONTROLLED STUDY; DNA REPAIR; HETEROCHROMATIN; HUMAN; HUMAN CELL; MULTIPLE MYELOMA; PRIORITY JOURNAL; PROTEIN METHYLATION; SILENCER GENE; TRANSCRIPTION INITIATION; TUMOR CELL LINE;

EID: 0030874380     PISSN: 02707306     EISSN: None     Source Type: Journal    
DOI: 10.1128/MCB.17.9.5612     Document Type: Article

References (36)

1. Boyes, J., and A. Bird. 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.
2. 6-methylguanine-DNA methyltransferase in mex-human cells. Cancer Res. 52:5257-5263.
3. 6-methylguanine-DNA methyltransferase in human normal and tumor tissue from brain, lung, and ovary. Cancer Res. 51:4131-4134.
4. Clark, S. J., J. Harrison, C. L. Paul, and M. Frommer. 1994. High sensitivity mapping of methylated cytosines. Nucleic Acids Res. 222:2990-2997.
5. Comb, M., and H. M. Goodman. 1990. CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2. Nucleic Acids Res. 18:3975-3982.
6. Costello, J. F., B. W. Futscher, R. A. Kroes, and R. O. Pieper. 1994. Methylation-related chromatin structure is associated with exclusion of transcription factors from and suppressed expression of the O-6-methylguanine DNA methyltransferase gene in human glioma cell lines. Mol. Cell. Biol. 14:6515-6521.
7. Costello, J. F., B. F. Futscher, K. Tano, D. M. Graunke, and R. O. Pieper. 1994. Graded methylation in the promoter and body of the O6-methylguanine-DNA methyltransferase (MGMT) gene correlates with MGMT expression in human glioma cells. J. Biol. Chcm. 269:17228-17237.
8. Day, R. S., III, C. H. J. Ziolkowski, D. A. Scudiero, S. A. Meyer, A. S. Lubiniecki, A. J. Girardi, S. M. Galloway, and G. D. Bynum. 1980. Defective repair of alkylated DNA by human tumour and SV40-transformed human cell strains. Nature 288:724-727.
9. Dolan, M. E., R. C. Moschel, and A. E. Pegg. 1990. Depletion of mammalian O6-alkylguanine-DNA alkyltransferase activity by O6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents. Proc. Natl. Acad. Sci. USA 87:5368-5372.
10. Erickson, L. C., G. Laurent, N. A. Sharkey, and K. W. Kohn. 1980. DNA cross-linking and monoadduct repair in nitrosourea-treated human tumor cells. Nature 288:727-729.
11. Futscher, B. W., K. Campbell, and W. S. Dalton. 1992. Collateral sensitivity to nitrosoureas in multidrug-resistant cells selected with verapamil. Cancer Res. 52:5013-5017.
12. Futscher, B. W., K. C. Micetich, D. M. Barnes, R. I. Fisher, and L. C. Erickson. 1989. Inhibition of DNA repair results in enhanced nitrosourea cytotoxicity in resistant human tumor cells. Cancer Commun. 1:65-73.
13. Gardiner-Garden, M., and M. Frommer. 1987. CpG islands in vetebrate genomes. J. Mol. Biol. 196:261-282.
14. Grunstein, M. 1990. Nucleosomes: regulators of transcription. Trends Genet. 6:395-400.
15. 6-methylguanine-DNA methyltransferase gene. Nucleic Acids Res. 19:6163-6167.
16. 6-methylguanine-DNA methyltransferase promoter reduces transcription. Biochim. Biophys. Acta 1217:141-146.
17. 6-methylguanine DNA methyltransferase gene. Nucleic Acids Res. 22:4614-4619.
18. Iguchi-Ariga, S. M. M., and W. Schaffner. 1989. CpG methylation of the cAMP-responsive enhancer/promoter sequence TGACGTCA abolishes specific factor binding as well as transcriptional activation. Genes Dev. 3:612-619.
19. Jost, J.-P., and J. Hofsteenge. 1992. The repressor MDBP-2 is a member of the histone H1 family that binds preferentially in vitro and in vivo to methylated nonspecific DNA sequences. Proc. Natl. Acad. Sci. USA 89:9499-9503.
20. Kamakaka, R. T., and J. O. Thomas. 1990. Chromatin structure of transcriptionally competent and repressed genes. EMBO J. 9:3997-4006.
21. 6-alkylguanine-DNA alkyltransferase expression in human brain tumours: possible significance in nitro-sourea therapy. Carcinogenesis 17:637-641.
22. Levine, A., A. Yeivin, E. Ben-Asher, Y. Aloni, and A. Razin. 1993. Histone H1-mediated inhibition of transcription initiation of methylated templates in vitro. J. Biol. Chem. 268:21754-21759.
23. 6-methylguanine-DNA methyltransferase in malignant human glioma cell lines. Carcinogenesis 12:1739-1744.
24. 6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. Cancer Res. 50:6119-6129.
25. 6-alkylguanine-DNA alkyltransferase. Prog. Nucleic Acid Res. Mol. Biol. 51:167-223.
26. Pieper, R. O. 1997. GenBank accession no. U95038.
27. Pieper, R. O., B. W. Futscher, Q. Dong, T. M. Ellis, and L. C. Erickson. 1990. Comparison of O-6-methylguanine DNA methyltransferase (MGMT) mRNA levels in Mer+ and Mer-human tumor cell lines containing the MGMT gene by the polymerase chain reaction technique. Cancer Commun. 2:13-20.
28. Pieper, R. O., S. Patel, S. A. Ting, Futscher, B. W., and J. F. Costello. 1996. Methylation of CpG island transcription factor binding sites is unnecessary for aberrant silencing of the human MGMT gene. J. Biol. Chem. 271:13916-13924.
29. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, p. 9.16-9.20. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
30. 6-methylguanine-DNA methyltransferase in histologically normal brain adjacent to primary human brain tumors. Proc. Natl. Acad. Sci. USA 93:6941-6946.
31. 6-methylguanine-DNA methyltransferase in human Mer+ and Mer-cells. Carcinogencsis 16:1857-1863.
32. Smith, D. G., and T. P. Brent. 1989. Response of cultured human cell lines from rhabdomyosarcoma xenografts to treatment with chloroethylnitrosoureas. Cancer Res. 49:883-886.
33. 6-alkylguanine. Proc. Natl. Acad. Sci. USA 87:686-690.
34. Watt, F., and P. L. Molloy. 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.
35. Wolffe, A. P. 1994. Transcription: in tune with the histones. Cell 77:13-16.
36. 6-alkylguanine-DNA alkyltransferase activity in human cells and tumor tissues by restriction enzyme inhibition. Cancer Res. 47:6229-6235.