DEV02302 Supplementary Material

Files in this Data Supplement:

• Supplemental Figure 1 -

  Fig. S1. Amino acid sequence alignment of human MLL and MLL2. Conserved regions, motifs and known globular domains are indicated with colored boxes. Domains in Pfam: AT-hooks (PF02178), zf-CXXC (PF02008), PHD fingers (PF00628), FYRN (PF05964), FYRC (PF05965), SET (PF00856). FYRN/C were first termed ATA1 and ATA2 (Prasad et al., 1997). Additional domains and motifs are indicated: ‘SNL-1’ and ‘SNL-2’ refers to regions conferring speckled nuclear localization (Yano et al., 1997); an extended PHD finger (ePHD), ‘TAD’ refers to a transactivation domain mapped in vitro (Prasad et al., 1995; Zeleznik-Le et al., 1994); and the postSET motif C-terminal refers to the SET domain. The two motifs indicated with red bars are the Taspase cleavage sites in MLL, one of which is also present in MLL2 (Yokoyama et al., 2002; Hsieh et al., 2003). The protein phosphatase 2A interaction motifs of MLL (Adler et al., 1997) are indicated below the alignment, as well as the fusion point, at amino acid 458, to β-galactosidase in the Yu allele (Yu et al., 1995). Other regions of homology are indicated in gray. The exon/intron boundaries are noted as arrows above and below the sequences.

  Additional references

  Adler, H. T., Nallaseth, F. S., Walter, G. and Tkachuk, D. C. (1997). HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A. J. Biol. Chem. 272, 28407-28414.

  Hsieh, J. J., Cheng, E. H. and Korsmeyer, S. J. (2003). Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression. Cell 115, 293-303.

  Prasad, R., Yano, T., Sorio, C., Nakamura, T., Rallapalli, R., Gu, Y., Leshkowitz, D., Croce, C. M. and Canaani, E. (1995). Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia. Proc. Natl. Acad. Sci. USA 92, 12160-12164.

  Prasad, R., Zhadanov, A. B., Sedkov, Y., Bullrich, F., Druck, T., Rallapalli, R., Yano, T., Alder, H., Croce, C. M., Huebner, K. et al. (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.

  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.

  Yokoyama, A., Kitabayashi, I., Ayton, P. M., Cleary, M. L. and Ohki, M. (2002). Leukemia proto-oncoprotein MLL is proteolytically processed into 2 fragments with opposite transcriptional properties. Blood 100, 3710-3718.

  Zeleznik-Le, N. J., Harden, A. M. and Rowley, J. D. (1994). 11q23 translocations split the ‘AT-hook’ cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. Proc. Natl. Acad. Sci. USA 91, 10610-10614.