Binding to Nonmethylated CpG DNA Is Essential for Target Recognition, Transactivation, and Myeloid Transformation by an MLL Oncoprotein

REFERENCES

• Armstrong, S. A., Staunton J. E., Silverman L. B., Pieters R., den Boer M. L., Minden M. D., Sallan S. E., Lander E. S., Golub T. R., and Korsmeyer S. J.. 2002. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat. Genet. 30:41–47.
   PubMed Web of Science ®Google Scholar
• Ayton, P., Sneddon S. F., Palmer D. B., Rosewell I. R., Owen M. J., Young B., Presley R., and Subramanian V.. 2001. Truncation of the Mll gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryos. Genesis 30:201–212.
   PubMedGoogle Scholar
• Ayton, P. M., and Cleary M. L.. 2001. Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene 20:5695–5707.
   PubMed Web of Science ®Google Scholar
• Ayton, P. M., and Cleary M. L.. 2003. Transformation of myeloid progenitors by MLL oncoproteins is dependent on Hoxa7 and Hoxa9. Genes Dev. 17:2298–2307.
   PubMed Web of Science ®Google Scholar
• Bird, A. 2002. DNA methylation patterns and epigenetic memory. Genes Dev. 16:6–21.
   PubMed Web of Science ®Google Scholar
• Birke, M., Schreiner S., Garcia-Cuellar M. P., Mahr K., Titgemeyer F., and Slany R. K.. 2002. The MT domain of the proto-oncoprotein MLL binds to CpG-containing DNA and discriminates against methylation. Nucleic Acids Res. 30:958–965.
   PubMed Web of Science ®Google Scholar
• Caldas, C., Kim M. H., MacGregor A., Cain D., Aparicio S., and Wiedemann L. M.. 1998. Isolation and characterization of a pufferfish MLL (mixed lineage leukemia)-like gene (fMll) reveals evolutionary conservation in vertebrate genes related to Drosophila trithorax. Oncogene 16:3233–3241.
   PubMedGoogle Scholar
• DiMartino, J. F., Ayton P. M., Chen E. H., Naftzger C. C., Young B. D., and Cleary M. L.. 2002. The AF10 leucine zipper is required for leukemic transformation of myeloid progenitors by MLL-AF10. Blood 99:3780–3785.
   PubMedGoogle Scholar
• DiMartino, J. F., Miller T., Ayton P. M., Landewe T., Hess J. L., Cleary M. L., and Shilatifard A.. 2000. A carboxy-terminal domain of ELL is required and sufficient for immortalization of myeloid progenitors by MLL-ELL. Blood 96:3887–3893.
   PubMedGoogle Scholar
• Djabali, M., Selleri L., Parry P., Bower M., Young B. D., and Evans G. A.. 1992. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat. Genet. 2:113–118.
   PubMed Web of Science ®Google Scholar
• Domer, P. H., Fakharzadeh S. S., Chen C. S., Jockel J., Johansen L., Silverman G. A., Kersey J. H., and Korsmeyer S. J.. 1993. Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product. Proc. Natl. Acad. Sci. USA 90:7884–7888.
   PubMed Web of Science ®Google Scholar
• Emerling, B. M., Bonifas J., Kratz C. P., Donovan S., Taylor B. R., Green E. D., Le Beau M. M., and Shannon K. M.. 2002. MLL5, a homolog of Drosophila trithorax located within a segment of chromosome band 7q22 implicated in myeloid leukemia. Oncogene 21:4849–4854.
   PubMed Web of Science ®Google Scholar
• FitzGerald, K. T., and Diaz M. O.. 1999. MLL2: a new mammalian member of the trx/MLL family of genes. Genomics 59:187–192.
   PubMed Web of Science ®Google Scholar
• Fujita, N., Shimotake N., Ohki I., Chiba T., Saya H., Shirakawa M., and Nakao M.. 2000. Mechanism of transcriptional regulation by methyl-CpG binding protein MBD1. Mol. Cell. Biol. 20:5107–5118.
   PubMed Web of Science ®Google Scholar
• Gu, Y., Nakamura T., Alder H., Prasad R., Canaani O., Cimino G., Croce C. M., and Canaani E.. 1992. The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. Cell 71:701–708.
   PubMed Web of Science ®Google Scholar
• Huntsman, D. G., Chin S. F., Muleris M., Batley S. J., Collins V. P., Wiedemann L. M., Aparicio S., and Caldas C.. 1999. MLL2, the second human homolog of the Drosophila trithorax gene, maps to 19q13.1 and is amplified in solid tumor cell lines. Oncogene 18:7975–7984.
   PubMed Web of Science ®Google Scholar
• Huth, J. R., Bewley C. A., Nissen M. S., Evans J. N., Reeves R., Gronenborn A. M., and Clore G. M.. 1997. The solution structure of an HMG-I(Y)-DNA complex defines a new architectural minor groove binding motif. Nat. Struct. Biol. 4:657–665.
   PubMedGoogle Scholar
• Lavau, C., Du C., Thirman M., and Zeleznik-Le N.. 2000. Chromatin-related properties of CBP fused to MLL generate a myelodysplastic-like syndrome that evolves into myeloid leukemia. EMBO J. 19:4655–4664.
   PubMed Web of Science ®Google Scholar
• Lavau, C., Szilvassy S. J., Slany R., and Cleary M. L.. 1997. Immortalization and leukemic transformation of a myelomonocytic precursor by retrovirally transduced HRX-ENL. EMBO J. 16:4226–4237.
   PubMed Web of Science ®Google Scholar
• Lawrence, H. J., Sauvageau G., Ahmadi N., Lopez A. R., LeBeau M. M., Link M., Humphries K., and Largman C.. 1995. Stage- and lineage-specific expression of the HOXA10 homeobox gene in normal and leukemic hematopoietic cells. Exp. Hematol. 23:1160–1166.
   PubMedGoogle Scholar
• Lee, J. H., Voo K. S., and Skalnik D. G.. 2001. Identification and characterization of the DNA binding domain of CpG-binding protein. J. Biol. Chem. 276:44669–44676.
   PubMed Web of Science ®Google Scholar
• Luo, R. T., Lavau C., Du C., Simone F., Polak P. E., Kawamata S., and Thirman M. J.. 2001. The elongation domain of ELL is dispensable but its ELL-associated factor 1 interaction domain is essential for MLL-ELL-induced leukemogenesis. Mol. Cell. Biol. 21:5678–5687.
   PubMed Web of Science ®Google Scholar
• Milne, T. A., Briggs S. D., Brock H. W., Martin M. E., Gibbs D., Allis C. D., and Hess J. L.. 2002. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol. Cell 10:1107–1117.
   PubMed Web of Science ®Google Scholar
• Nakamura, T., Mori T., Tada S., Krajewski W., Rozovskaia T., Wassell R., Dubois G., Mazo A., Croce C. M., and Canaani E.. 2002. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol. Cell 10:1119–1128.
   PubMed Web of Science ®Google Scholar
• Pineault, N., Helgason C. D., Lawrence H. J., and Humphries R. K.. 2002. Differential expression of Hox, Meis1, and Pbx1 genes in primitive cells throughout murine hematopoietic ontogeny. Exp. Hematol. 30:49–57.
   PubMedGoogle Scholar
• Prasad, R., Zhadanov A. B., Sedkov Y., Bullrich F., Druck T., Rallapalli R., Yano T., Alder H., Croce C. M., Huebner K., Mazo A., and Canaani E.. 1997. Structure and expression pattern of human ALR, a novel gene with strong homology to ALL-1 involved in acute leukemia and to Drosophila trithorax. Oncogene 15:549–560.
   PubMed Web of Science ®Google Scholar
• Rozovskaia, T., Feinstein E., Mor O., Foa R., Blechman J., Nakamura T., Croce C. M., Cimino G., and Canaani E.. 2001. Upregulation of Meis1 and HoxA9 in acute lymphocytic leukemias with the t(4: 11) abnormality. Oncogene 20:874–878.
   PubMed Web of Science ®Google Scholar
• Ruault, M., Brun M. E., Ventura M., Roizes G., and De Sario A.. 2002. MLL3, a new human member of the TRX/MLL gene family, maps to 7q36, a chromosome region frequently deleted in myeloid leukaemia. Gene 284:73–81.
   PubMed Web of Science ®Google Scholar
• Sauvageau, G., Lansdorp P. M., Eaves C. J., Hogge D. E., Dragowska W. H., Reid D. S., Largman C., Lawrence H. J., and Humphries R. K.. 1994. Differential expression of homeobox genes in functionally distinct CD34+ subpopulations of human bone marrow cells. Proc. Natl. Acad. Sci. USA 91:12223–12227.
   PubMed Web of Science ®Google Scholar
• Schreiner, S. A., Garcia-Cuellar M. P., Fey G. H., and Slany R. K.. 1999. The leukemogenic fusion of MLL with ENL creates a novel transcriptional transactivator. Leukemia 13:1525–1533.
   PubMedGoogle Scholar
• Schumacher, A., and Magnuson T.. 1997. Murine Polycomb- and trithorax-group genes regulate homeotic pathways and beyond. Trends Genet. 13:167–170.
   PubMed Web of Science ®Google Scholar
• Slany, R. K., Lavau C., and Cleary M. L.. 1998. The oncogenic capacity of HRX-ENL requires the transcriptional transactivation activity of ENL and the DNA binding motifs of HRX. Mol. Cell. Biol. 18:122–129.
   PubMed Web of Science ®Google Scholar
• So, C. W., and Cleary M. L.. 2002. MLL-AFX requires the transcriptional effector domains of AFX to transform myeloid progenitors and transdominantly interfere with forkhead protein function. Mol. Cell. Biol. 22:6542–6552.
   PubMed Web of Science ®Google Scholar
• So, C. W., and Cleary M. L.. 2003. Common mechanism for oncogenic activation of MLL by forkhead family proteins. Blood 101:633–639.
   PubMedGoogle Scholar
• So, C. W., Lin M., Ayton P. M., Chen E. H., and Cleary M. L.. 2003. Dimerization contributes to oncogenic activation of MLL chimeras in acute leukemias. Cancer Cell 4:99–110.
   PubMedGoogle Scholar
• Strahl, B. D., Ohba R., Cook R. G., and Allis C. D.. 1999. Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in Tetrahymena. Proc. Natl. Acad. Sci. USA 96:14967–14972.
   PubMed Web of Science ®Google Scholar
• Tkachuk, D. C., Kohler S., and Cleary M. L.. 1992. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell 71:691–700.
   PubMed Web of Science ®Google Scholar
• Yagi, H., Deguchi K., Aono A., Tani Y., Kishimoto T., and Komori T.. 1998. Growth disturbance in fetal liver hematopoiesis of Mll-mutant mice. Blood 92:108–117.
   PubMed Web of Science ®Google Scholar
• Yano, T., Nakamura T., Blechman J., Sorio C., Dang C. V., Geiger B., and Canaani E.. 1997. Nuclear punctate distribution of ALL-1 is conferred by distinct elements at the N terminus of the protein. Proc. Natl. Acad. Sci. USA 94:7286–7291.
   PubMed Web of Science ®Google Scholar
• Yeoh, E. J., Ross M. E., Shurtleff S. A., Williams W. K., Patel D., Mahfouz R., Behm F. G., Raimondi S. C., Relling M. V., Patel A., Cheng C., Campana D., Wilkins D., Zhou X., Li J., Liu H., Pui C. H., Evans W. E., Naeve C., Wong L., and Downing J. R.. 2002. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1:133–143.
   PubMed Web of Science ®Google Scholar
• Yu, B. D., Hanson R. D., Hess J. L., Horning S. E., and Korsmeyer S. J.. 1998. MLL, a mammalian trithorax-group gene, functions as a transcriptional maintenance factor in morphogenesis. Proc. Natl. Acad. Sci. USA 95:10632–10636.
   PubMed Web of Science ®Google Scholar
• Yu, B. D., Hess J. L., Horning S. E., Brown G. A., and Korsmeyer S. J.. 1995. Altered Hox expression and segmental identity in Mll-mutant mice. Nature 378:505–508.
   PubMed Web of Science ®Google Scholar
• Zeisig, B. B., Schreiner S., Garcia-Cuellar M. P., and Slany R. K.. 2003. Transcriptional activation is a key function encoded by MLL fusion partners. Leukemia 17:359–365.
   PubMedGoogle Scholar