Alternative titles; symbols
HGNC Approved Gene Symbol: MYBL2
Cytogenetic location: 20q13.12 Genomic coordinates (GRCh38): 20:43,667,114-43,716,482 (from NCBI)
The MYBL2 gene belongs to the MYB family of transcription factor genes and plays an essential role during cell cycle progression. MYBL2 transcripts are detectable in a wide variety of dividing cell types. MYBL2 activates CDC2 (116940) and cyclin D1 (168461) gene expression in proliferating fibroblasts, and antisense oligonucleotides specific to MYBL2 inhibit proliferation of human hematopoietic cell lines. MYBL2 expression is also regulated at the G1/S phase transition, and its transcription relies on E2F (189971) activity in a cell cycle-dependent manner. Thus, unlike MYB (189990) and MYBL1 (159405), whose transcriptional activity is mainly restricted to hematopoietic, spermatogenic, and neural progenitor cells, MYBL2 appears to possess a broader function during cell proliferation (Noben-Trauth et al., 1996).
Lang et al. (2005) identified 3 BMYB-binding sites in a DNase I-hypersensitive site near the junction of exon 2 and intron 2 in the BCL2 gene (151430). Antisense BMYB downregulated BCL2 and led to apoptosis of a BCL2-expressing B-cell line. Lang et al. (2005) proposed that BMYB is essential for B-cell survival.
By gel filtration of MOLT-4 human T cells, Schmit et al. (2007) identified BMYB as a subunit of the over 669-kD LIN complex. Other stable LIN complex components included LIN9 (609375), LIN37, LIN54 (613367), and RBAP48 (RBBP4; 602923). All endogenous or epitope-tagged LIN complex subunits coimmunoprecipitated with one another, and all were efficiently codepleted together with antibodies directed to LIN9. The LIN complex associated with E2F (see 189971)-regulated promoters in the T98G human glioblastoma cell line and was required for activation of G2/M genes. Depletion of LIN complex subunits had no significant effect on expression of G1/S genes.
By a combination of Southern blot analysis of somatic cell hybrid DNAs and in situ hybridization, Barletta et al. (1991) assigned the MYBL2 gene to chromosome Xq13. However, Noben-Trauth et al. (1996) demonstrated that this assignment was an error. Using mouse Mybl2 cDNA clones as probes, they assigned Mybl2 in an interspecific backcross panel to distal mouse chromosome 2. Using human cDNA probes in combination with fluorescence in situ hybridization analysis, they localized MYBL2 to chromosome 20q13.1, a region that is commonly deleted in myeloid disorders and shows high homology of synteny to mouse chromosome 2. Noben-Trauth et al. (1996) stated that the reason for the discrepancy between the 2 mapping studies was not clear.
Manak et al. (2002) noted that, in addition to MYB, 2 MYB-related genes, AMYB (MYBL1) and BMYB (MYBL2), are present in vertebrates. Drosophila has a single Myb gene most closely related to BMYB. Manak et al. (2002) isolated 2 late-larval lethal alleles of Drosophila Myb. Mutant mitotic cells displayed a variety of abnormalities, suggesting that the absence of Drosophila Myb causes a defect in S phase that may result in M-phase abnormalities. Consistent with a role for Drosophila Myb during S phase, Manak et al. (2002) detected Drosophila Myb protein in S-phase nuclei of wildtype mitotic cells as well as endocycling cells, which lack both an M phase and cyclin B expression. Moreover, they found that the Drosophila Myb protein is concentrated in regions of S-phase nuclei that are actively undergoing DNA replication. Together these findings implied that Drosophila Myb provides an essential nontranscriptional function during chromosomal replication.
Shepard et al. (2005) identified a zebrafish cell proliferation mutant, 'crash and burn' (crb), that resulted from a loss-of-function mutation in Bmyb. They found that crb embryos had defects in mitotic progression and spindle formation and exhibited genome instability. Regulation of cyclin B (123836) levels by Bmyb appeared to be the mechanism of mitotic accumulation in crb mutants. Adult crb heterozygotes had increased cancer susceptibility.
Barletta, C., Druck, T., LaForgia, S., Calabretta, B., Drabkin, H., Patterson, D., Croce, C. M., Huebner, K. Chromosome locations of the MYB related genes, AMYB and BMYB. Cancer Res. 51: 3821-3824, 1991. [PubMed: 2065336]
Lang, G., Gombert, W. M., Gould, H. J. A transcriptional regulatory element in the coding sequence of the human Bcl-2 gene. Immunology 114: 25-36, 2005. [PubMed: 15606792] [Full Text: https://doi.org/10.1111/j.1365-2567.2004.02073.x]
Manak, J. R., Mitiku, N., Lipsick, J. S. Mutation of the Drosophila homologue of the Myb protooncogene causes genomic instability. Proc. Nat. Acad. Sci. 99: 7438-7443, 2002. [PubMed: 12032301] [Full Text: https://doi.org/10.1073/pnas.122231599]
Noben-Trauth, K., Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Sonoda, G., Testa, J. R., Klempnauer, K.-H. Mybl2 (Bmyb) maps to mouse chromosome 2 and human chromosome 20q13.1. Genomics 35: 610-612, 1996. [PubMed: 8812502] [Full Text: https://doi.org/10.1006/geno.1996.0408]
Schmit, F., Korenjak, M., Mannefeld, M., Schmitt, K., Franke, C., von Eyss, B., Gagrica, S., Hanel, F., Brehm,A., Gaubatz, S. LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes. Cell Cycle 6: 1903-19113, 2007. [PubMed: 17671431] [Full Text: https://doi.org/10.4161/cc.6.15.4512]
Shepard, J. L., Amatruda, J. F., Stern, H. M., Subramanian, A., Finkelstein, D., Ziai, J., Finley, K. R., Pfaff, K. L., Hersey, C., Zhou, Y., Barut, B., Freedman, M., and 9 others. A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility. Proc. Nat. Acad. Sci. 102: 13194-13199, 2005. [PubMed: 16150706] [Full Text: https://doi.org/10.1073/pnas.0506583102]