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. 1993 May 11;21(9):2125–2130. doi: 10.1093/nar/21.9.2125

Identification of two novel mouse nuclear proteins that bind selectively to a methylated c-Myc recognizing sequence.

I Suetake 1, S Tajima 1, A Asano 1
PMCID: PMC309474  PMID: 8502552

Abstract

The c-Myc recognizes the sequence CACGTG (Blackwell, T. K., Kretzner, L., Blackwood, E.M., Eisenman, R. N., and Weintraub, H. (1990) Science 250, 1149-1151), and its binding is inhibited by methylation of the core CpG (Prendergast, G. C. and Ziff, E. B. (1991) Science 251, 186-189). We identified two novel nuclear proteins, MMBP-1 and MMBP-2, that bound specifically and under physiological salt condition to the c-Myc binding motif of which cytidine in the CpG sequence was methylated. MMBP-1 was about 42 kD and MMBP-2 was about 63 kD. MMBP-1 was found in specific cells, while MMBP-2 was found in all the cell lines tested, suggesting that MMBP-1 may modulate the role of MMBP-2 in tissue specific manner. We propose that the two proteins play a role in the regulation of c-Myc function through stabilizing or destabilizing the methylation state of the c-Myc binding motif.

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Selected References

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

  1. Amati B., Dalton S., Brooks M. W., Littlewood T. D., Evan G. I., Land H. Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max. Nature. 1992 Oct 1;359(6394):423–426. doi: 10.1038/359423a0. [DOI] [PubMed] [Google Scholar]
  2. Beckmann H., Su L. K., Kadesch T. TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif. Genes Dev. 1990 Feb;4(2):167–179. doi: 10.1101/gad.4.2.167. [DOI] [PubMed] [Google Scholar]
  3. Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
  4. Blackwell T. K., Kretzner L., Blackwood E. M., Eisenman R. N., Weintraub H. Sequence-specific DNA binding by the c-Myc protein. Science. 1990 Nov 23;250(4984):1149–1151. doi: 10.1126/science.2251503. [DOI] [PubMed] [Google Scholar]
  5. Boyes J., Bird A. DNA methylation inhibits transcription indirectly via a methyl-CpG binding protein. Cell. 1991 Mar 22;64(6):1123–1134. doi: 10.1016/0092-8674(91)90267-3. [DOI] [PubMed] [Google Scholar]
  6. 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 Jan;11(1):327–333. doi: 10.1002/j.1460-2075.1992.tb05055.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cedar H. DNA methylation and gene activity. Cell. 1988 Apr 8;53(1):3–4. doi: 10.1016/0092-8674(88)90479-5. [DOI] [PubMed] [Google Scholar]
  8. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dynan W. S., Tjian R. Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II. Cell. 1983 Mar;32(3):669–680. doi: 10.1016/0092-8674(83)90053-3. [DOI] [PubMed] [Google Scholar]
  10. Foulkes N. S., Borrelli E., Sassone-Corsi P. CREM gene: use of alternative DNA-binding domains generates multiple antagonists of cAMP-induced transcription. Cell. 1991 Feb 22;64(4):739–749. doi: 10.1016/0092-8674(91)90503-q. [DOI] [PubMed] [Google Scholar]
  11. Gregor P. D., Sawadogo M., Roeder R. G. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev. 1990 Oct;4(10):1730–1740. doi: 10.1101/gad.4.10.1730. [DOI] [PubMed] [Google Scholar]
  12. Jost J. P., Hofsteenge J. 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 U S A. 1992 Oct 15;89(20):9499–9503. doi: 10.1073/pnas.89.20.9499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kretzner L., Blackwood E. M., Eisenman R. N. Myc and Max proteins possess distinct transcriptional activities. Nature. 1992 Oct 1;359(6394):426–429. doi: 10.1038/359426a0. [DOI] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Lewis J. D., Meehan R. R., Henzel W. J., Maurer-Fogy I., Jeppesen P., Klein F., Bird A. Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. Cell. 1992 Jun 12;69(6):905–914. doi: 10.1016/0092-8674(92)90610-o. [DOI] [PubMed] [Google Scholar]
  16. Lüscher B., Eisenman R. N. New light on Myc and Myb. Part I. Myc. Genes Dev. 1990 Dec;4(12A):2025–2035. doi: 10.1101/gad.4.12a.2025. [DOI] [PubMed] [Google Scholar]
  17. Meehan R. R., Lewis J. D., Bird A. P. Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucleic Acids Res. 1992 Oct 11;20(19):5085–5092. doi: 10.1093/nar/20.19.5085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Meehan R. R., Lewis J. D., McKay S., Kleiner E. L., Bird A. P. Identification of a mammalian protein that binds specifically to DNA containing methylated CpGs. Cell. 1989 Aug 11;58(3):499–507. doi: 10.1016/0092-8674(89)90430-3. [DOI] [PubMed] [Google Scholar]
  19. Paroush Z., Keshet I., Yisraeli J., Cedar H. Dynamics of demethylation and activation of the alpha-actin gene in myoblasts. Cell. 1990 Dec 21;63(6):1229–1237. doi: 10.1016/0092-8674(90)90418-e. [DOI] [PubMed] [Google Scholar]
  20. Pawlak A., Bryans M., Jost J. P. An avian 40 KDa nucleoprotein binds preferentially to a promoter sequence containing one single pair of methylated CpG. Nucleic Acids Res. 1991 Mar 11;19(5):1029–1034. doi: 10.1093/nar/19.5.1029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Prendergast G. C., Lawe D., Ziff E. B. Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Cell. 1991 May 3;65(3):395–407. doi: 10.1016/0092-8674(91)90457-a. [DOI] [PubMed] [Google Scholar]
  22. Prendergast G. C., Ziff E. B. Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region. Science. 1991 Jan 11;251(4990):186–189. doi: 10.1126/science.1987636. [DOI] [PubMed] [Google Scholar]
  23. Razin A., Cedar H. DNA methylation and gene expression. Microbiol Rev. 1991 Sep;55(3):451–458. doi: 10.1128/mr.55.3.451-458.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Razin A., Szyf M., Kafri T., Roll M., Giloh H., Scarpa S., Carotti D., Cantoni G. L. Replacement of 5-methylcytosine by cytosine: a possible mechanism for transient DNA demethylation during differentiation. Proc Natl Acad Sci U S A. 1986 May;83(9):2827–2831. doi: 10.1073/pnas.83.9.2827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Saluz H. P., Jiricny J., Jost J. P. Genomic sequencing reveals a positive correlation between the kinetics of strand-specific DNA demethylation of the overlapping estradiol/glucocorticoid-receptor binding sites and the rate of avian vitellogenin mRNA synthesis. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7167–7171. doi: 10.1073/pnas.83.19.7167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  27. Wang R. Y., Zhang X. Y., Khan R., Zhou Y. W., Huang L. H., Ehrlich M. Methylated DNA-binding protein from human placenta recognizes specific methylated sites on several prokaryotic DNAs. Nucleic Acids Res. 1986 Dec 22;14(24):9843–9860. doi: 10.1093/nar/14.24.9843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Watanabe T., Oishi M. Dimethyl sulfoxide-inducible cytoplasmic factor involved in erythroid differentiation in mouse erythroleukemia (Friend) cells. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6481–6485. doi: 10.1073/pnas.84.18.6481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zhang X. Y., Asiedu C. K., Supakar P. C., Khan R., Ehrlich K. C., Ehrlich M. Binding sites in mammalian genes and viral gene regulatory regions recognized by methylated DNA-binding protein. Nucleic Acids Res. 1990 Nov 11;18(21):6253–6260. doi: 10.1093/nar/18.21.6253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zhang X. Y., Supakar P. C., Khan R., Ehrlich K. C., Ehrlich M. Related sites in human and herpesvirus DNA recognized by methylated DNA-binding protein from human placenta. Nucleic Acids Res. 1989 Feb 25;17(4):1459–1474. doi: 10.1093/nar/17.4.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Zingg J. M., Alva G. P., Jost J. P. Characterisation of a genomic clone covering the structural mouse MyoD1 gene and its promoter region. Nucleic Acids Res. 1991 Dec 11;19(23):6433–6439. doi: 10.1093/nar/19.23.6433. [DOI] [PMC free article] [PubMed] [Google Scholar]

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