Alternative titles; symbols
HGNC Approved Gene Symbol: BCL9
Cytogenetic location: 1q21.2 Genomic coordinates (GRCh38): 1:147,541,501-147,626,216 (from NCBI)
Studying a cell line (CEMO-1) from a patient with precursor-B-cell acute lymphoblastic leukemia with a t(1;14)(q21;q32), Willis et al. (1998) identified a fusion partner of the IGHJ gene (147010) on 14q. One allele showed novel sequences upstream of JH5 with no homology to either IGH or any other sequence in databases. Using a single-copy restriction fragment immediately 5-prime of JH5, PAC clones were isolated and mapped to 1q21 on normal metaphases by fluorescence in situ hybridization, confirming that this allele represented the translocation breakpoint. Sequence analysis of the 1q21 restriction fragment showed identity with an expressed sequenced tag, and this probe was therefore used to probe Northern blots. Willis et al. (1998) designated the gene on 1q21 BCL9. Sequence analysis predicted a protein of 1,394 amino acids, with no recognizable protein motifs or significant homologies to known proteins. The CEMO-1 1q21 breakpoint fell within the 3-prime untranslated region (UTR) of the BCL9 gene. By screening of a panel of 39 B-cell malignancies with 1q abnormalities by Southern blotting, Willis et al. (1998) found 1 additional case with a breakpoint in the 3-prime UTR of BCL9, indicating that this is a recurrent breakpoint. Fluorescence in situ hybridization analysis using an 850-kb YAC spanning BCL9 identified a further case of t(1;22)(q21;q11) causing juxtaposition of BCL9 to the IGL locus (147220).
By analysis of a translocation t(1;14)(q21;q32) breakpoint, Willis et al. (1998) mapped the BCL9 gene to chromosome 1q21.
WNT (see 602863) signaling controls many fundamental processes during animal development. WNT transduction is mediated by the association of beta-catenin (116806) with nuclear TCF (e.g., LEF1; 153245) DNA-binding factors. Kramps et al. (2002) identified 2 segment polarity genes in Drosophila, legless (Lgs), and pygopus (Pygo), and showed that their products are required for WNT signal transduction at the level of nuclear beta-catenin. Lgs encodes the homolog of human BCL9, and the authors provided genetic and molecular evidence that these proteins exert their function by physically linking Pygo to beta-catenin. Kramps et al. (2002) identified 2 human homologs of the Drosophila Pygo gene, PYGO1 (606902)and PYGO2 (606903), that possess a highly conserved PHD finger that interacts with homology domain-1 (HD1) of BCL9. The findings suggested that the recruitment of PYGO permits beta-catenin to transcriptionally activate WNT target genes and raised the possibility that a deregulation of these events may play a causal role in the development of B-cell malignancies.
Kramps, T., Peter, O., Brunner, E., Nellen, D., Froesch, B., Chatterjee, S., Murone, M., Zullig, S., Basler, K. Wnt/Wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell 109: 47-60, 2002. [PubMed: 11955446] [Full Text: https://doi.org/10.1016/s0092-8674(02)00679-7]
Willis, T. G., Zalcberg, I. R., Coignet, L. J. A., Wlodarska, M., Stul, D. M., Jadayel, D. M., Bastard, C., Treleaven, J. G., Catovsky, D., Silva, M. L. M., Dyer, M. J. S. Molecular cloning of translocation t(1;14)(q21;q32) defines a novel gene (BCL9) at chromosome 1q21. Blood 91: 1873-1881, 1998. [PubMed: 9490669]