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Gene Review

L3MBTL1  -  l(3)mbt-like 1 (Drosophila)

Homo sapiens

Synonyms: DKFZp586P1522, H-L(3)MBT, H-l(3)mbt, H-l(3)mbt protein, KIAA0681, ...
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Disease relevance of L3MBTL


High impact information on L3MBTL

  • MBT-1 structurally resembles the H-L(3)MBT protein, whose deletion is predicted to be responsible for myeloid hematopoietic malignancies [2].
  • L3MBTL lies in a region of chromosome 20, deletion of which is associated with myeloid malignancies and represents a good candidate for a 20q target gene [3].
  • Here we demonstrate that monoallelic methylation of two CpG islands correlates with transcriptional silencing of L3MBTL, and that L3MBTL transcription occurs from the paternally derived allele in five individuals from two families [3].
  • We found that H-L(3)MBT binds in vivo to TEL, and we have mapped the region of interaction to their respective SPM/SAM domains [4].
  • H-L(3)MBT acts as a histone deacetylase-independent transcriptional repressor, based on its lack of sensitivity to trichostatin A [4].

Associations of L3MBTL with chemical compounds

  • In both the "cavity insertion" (L3MBTL1) and "surface groove" (PHD finger) modes of methyllysine recognition, a carboxylate group both hydrogen bonds and ion pairs to the methylammonium proton [5].
  • Consistent with this, we found that the L3MBTL1 MBT domains compact nucleosomal arrays dependent on mono- and dimethylation of histone H4 lysine 20 and of histone H1b lysine 26 [6].

Biological context of L3MBTL


Anatomical context of L3MBTL


  1. Structural integrity and expression of the L3MBTL gene in normal and malignant hematopoietic cells. MacGrogan, D., Kalakonda, N., Alvarez, S., Scandura, J.M., Boccuni, P., Johansson, B., Nimer, S.D. Genes Chromosomes Cancer (2004) [Pubmed]
  2. Impaired maturation of myeloid progenitors in mice lacking novel Polycomb group protein MBT-1. Arai, S., Miyazaki, T. EMBO J. (2005) [Pubmed]
  3. Imprinting of the human L3MBTL gene, a polycomb family member located in a region of chromosome 20 deleted in human myeloid malignancies. Li, J., Bench, A.J., Vassiliou, G.S., Fourouclas, N., Ferguson-Smith, A.C., Green, A.R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. The human L(3)MBT polycomb group protein is a transcriptional repressor and interacts physically and functionally with TEL (ETV6). Boccuni, P., MacGrogan, D., Scandura, J.M., Nimer, S.D. J. Biol. Chem. (2003) [Pubmed]
  5. Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger. Li, H., Fischle, W., Wang, W., Duncan, E.M., Liang, L., Murakami-Ishibe, S., Allis, C.D., Patel, D.J. Mol. Cell (2007) [Pubmed]
  6. L3MBTL1, a histone-methylation-dependent chromatin lock. Trojer, P., Li, G., Sims, R.J., Vaquero, A., Kalakonda, N., Boccuni, P., Lee, D., Erdjument-Bromage, H., Tempst, P., Nimer, S.D., Wang, Y.H., Reinberg, D. Cell (2007) [Pubmed]
  7. L3mbtl, the mouse orthologue of the imprinted L3MBTL, displays a complex pattern of alternative splicing and escapes genomic imprinting. Li, J., Bench, A.J., Piltz, S., Vassiliou, G., Baxter, E.J., Ferguson-Smith, A.C., Green, A.R. Genomics (2005) [Pubmed]
  8. Characterization of the imprinted polycomb gene L3MBTL, a candidate 20q tumour suppressor gene, in patients with myeloid malignancies. Bench, A.J., Li, J., Huntly, B.J., Delabesse, E., Fourouclas, N., Hunt, A.R., Deloukas, P., Green, A.R. Br. J. Haematol. (2004) [Pubmed]
  9. A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes. Koga, H., Matsui, S., Hirota, T., Takebayashi, S., Okumura, K., Saya, H. Oncogene (1999) [Pubmed]
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