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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Gene Review: 

KMT2C  -  lysine (K)-specific methyltransferase 2C

Homo sapiens

Synonyms: HALR, Histone-lysine N-methyltransferase 2C, Homologous to ALR protein, KIAA1506, Lysine N-methyltransferase 2C, ...
 
 
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High impact information on MLL3

  • These results suggest that ASC-2 confers target gene specificity to MLL3 and MLL4 H3K4MT complexes and that recruitment of H3K4MTs to their target genes generally involves interactions between integral components of H3K4MT complexes and transcription factors [1].
  • ASCOM contains retinoblastoma-binding protein RBQ-3, alpha/beta-tubulins, and trithorax group proteins ALR-1, ALR-2, HALR, and ASH2 [2].
  • In particular, ALR-1/2 and HALR contain a highly conserved 130- to 140-amino-acid motif termed the SET domain, which was recently implicated in histone H3 lysine-specific methylation activities [2].
  • Indeed, recombinant ALR-1, HALR, and immunopurified ASCOM exhibit very weak but specific H3-lysine 4 methylation activities in vitro, and transactivation by retinoic acid receptor appears to involve ligand-dependent recruitment of ASCOM and subsequent transient H3-lysine 4 methylation of the promoter region in vivo [2].
  • Reverse transcription-PCR analysis carried out in six patients showed a 5' MLL-3' AF-10 fusion transcript [3].
 

Biological context of MLL3

  • Interestingly, PHD and SET domains are frequently found in proteins encoded by genes that are rearranged in different haematological malignancies and MLL3 maps to 7q36, a chromosome region that is frequently deleted in myeloid disorders [4].
  • Taking into consideration its notable protein motifs, ubiquitous expression, evolutionary conservation and chromosomal position, HALR is likely to play a housekeeping role in transcriptional regulation, and may be involved in leukemogenesis and developmental disorders [5].
  • The HALR gene contains 46 exons, is estimated to span >101 kb, and is located on chromosome region 7q36 [5].
 

Anatomical context of MLL3

 

Other interactions of MLL3

  • We characterized MLL3, a new human member of the TRX/MLL gene family [4].
  • The duplicated region contained a fragment of the MLL3 gene, which, after juxtacentromeric reshuffling, generated the ancestral BAGE gene [6].

References

  1. Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases. Lee, S., Lee, D.K., Dou, Y., Lee, J., Lee, B., Kwak, E., Kong, Y.Y., Lee, S.K., Roeder, R.G., Lee, J.W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Activating signal cointegrator 2 belongs to a novel steady-state complex that contains a subset of trithorax group proteins. Goo, Y.H., Sohn, Y.C., Kim, D.H., Kim, S.W., Kang, M.J., Jung, D.J., Kwak, E., Barlev, N.A., Berger, S.L., Chow, V.T., Roeder, R.G., Azorsa, D.O., Meltzer, P.S., Suh, P.G., Song, E.J., Lee, K.J., Lee, Y.C., Lee, J.W. Mol. Cell. Biol. (2003) [Pubmed]
  3. Breakpoint heterogeneity in t(10;11) translocation in AML-M4/M5 resulting in fusion of AF10 and MLL is resolved by fluorescent in situ hybridization analysis. Beverloo, H.B., Le Coniat, M., Wijsman, J., Lillington, D.M., Bernard, O., de Klein, A., van Wering, E., Welborn, J., Young, B.D., Hagemeijer, A. Cancer Res. (1995) [Pubmed]
  4. MLL3, a new human member of the TRX/MLL gene family, maps to 7q36, a chromosome region frequently deleted in myeloid leukaemia. Ruault, M., Brun, M.E., Ventura, M., Roizès, G., De Sario, A. Gene (2002) [Pubmed]
  5. Novel human HALR (MLL3) gene encodes a protein homologous to ALR and to ALL-1 involved in leukemia, and maps to chromosome 7q36 associated with leukemia and developmental defects. Tan, Y.C., Chow, V.T. Cancer Detect. Prev. (2001) [Pubmed]
  6. BAGE genes generated by juxtacentromeric reshuffling in the Hominidae lineage are under selective pressure. Ruault, M., Ventura, M., Galtier, N., Brun, M.E., Archidiacono, N., Roizès, G., De Sario, A. Genomics (2003) [Pubmed]
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