Genomes and Genes
Gene Symbol: L3MBTL1
Description: L3MBTL1, histone methyl-lysine binding protein
Alias: H-L(3)MBT, L3MBTL, ZC2HC3, dJ138B7.3, lethal(3)malignant brain tumor-like protein 1, l(3)mbt protein homolog, l(3)mbt-like 1, lethal (3) malignant brain tumor l(3)
- Sonoda M, Ishimura M, Ichimiya Y, Terashi E, Eguchi K, Sakai Y, et al. Atypical erythroblastosis in a patient with Diamond-Blackfan anemia who developed del(20q) myelodysplasia. Int J Hematol. 2018;108:228-231 pubmed publisher..2q13.3). Severe anemia required transfusions. Del(20q), including the L3MBTL1 gene, is reported to be relevant to the hematological phenotype of Shwachman-Diamond syndrome...
- Hoya Arias R, Tomishima M, Perna F, Voza F, Nimer S. L3MBTL1 deficiency directs the differentiation of human embryonic stem cells toward trophectoderm. Stem Cells Dev. 2011;20:1889-900 pubmed publisher..To define how L3MBTL1, a chromatin-associated polycomb group protein with transcriptional repressive activities, regulates early events ..
- Saddic L, West L, Aslanian A, Yates J, Rubin S, Gozani O, et al. Methylation of the retinoblastoma tumor suppressor by SMYD2. J Biol Chem. 2010;285:37733-40 pubmed publisher..at lysine 860 provides a direct binding site for the methyl-binding domain of the transcriptional repressor L3MBTL1. These results support the idea that a code of post-translational modifications exists for RB and helps guide its ..
- West L, Roy S, Lachmi Weiner K, Hayashi R, Shi X, Appella E, et al. The MBT repeats of L3MBTL1 link SET8-mediated p53 methylation at lysine 382 to target gene repression. J Biol Chem. 2010;285:37725-32 pubmed publisher..recognition of p53K382me1 by the triple malignant brain tumor (MBT) repeats of the chromatin compaction factor L3MBTL1. We demonstrate that SET8-mediated methylation of p53 at Lys-382 promotes the interaction between L3MBTL1 and p53 ..
- Feichtinger J, Larcombe L, McFarlane R. Meta-analysis of expression of l(3)mbt tumor-associated germline genes supports the model that a soma-to-germline transition is a hallmark of human cancers. Int J Cancer. 2014;134:2359-65 pubmed publisher..This has implications for our understanding of human oncogenesis and the development of new therapeutic and biomarker targets with clinical potential...
- Boccuni P, MacGrogan D, Scandura J, Nimer S. The human L(3)MBT polycomb group protein is a transcriptional repressor and interacts physically and functionally with TEL (ETV6). J Biol Chem. 2003;278:15412-20 pubmed..We speculate that the interaction of TEL with H-L(3)MBT can direct a PcG complex to genes repressed by TEL, stabilizing their repressed state. ..
- Sims J, Rice J. PR-Set7 establishes a repressive trans-tail histone code that regulates differentiation. Mol Cell Biol. 2008;28:4459-68 pubmed publisher..histone code is involved in a transcriptional regulatory pathway in vivo whereby monomethylated H4K20 binds the L3MBTL1 repressor protein to repress specific genes, including RUNX1, a critical regulator of hematopoietic ..
- Bench A, Li J, Huntly B, Delabesse E, Fourouclas N, Hunt A, et al. Characterization of the imprinted polycomb gene L3MBTL, a candidate 20q tumour suppressor gene, in patients with myeloid malignancies. Br J Haematol. 2004;127:509-18 pubmedChromosome 20q deletion is a recurrent chromosomal abnormality associated with myeloid malignancies. L3MBTL represents a strong candidate tumour suppressor gene since it lies within the common deleted region, is a member of the Polycomb-..
- Boehm D, Jeng M, Camus G, Gramatica A, Schwarzer R, Johnson J, et al. SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency. Cell Host Microbe. 2017;21:569-579.e6 pubmed publisher..Further, we find that lethal 3 malignant brain tumor 1 (L3MBTL1), a reader protein with chromatin-compacting properties that recognizes H4K20me1, was recruited to the latent HIV-..
- Nacci L, Valli R, Maria Pinto R, Zecca M, Cipolli M, Morini J, et al. Parental origin of the deletion del(20q) in Shwachman-Diamond patients and loss of the paternally derived allele of the imprinted L3MBTL1 gene. Genes Chromosomes Cancer. 2017;56:51-58 pubmed publisher..We collected 6 SDS cases with del(20q): a cluster of imprinted genes, including L3MBTL1 and SGK2 is present in the deleted region. Only the paternal allele is expressed for these genes...
- Acs K, Luijsterburg M, Ackermann L, Salomons F, Hoppe T, Dantuma N. The AAA-ATPase VCP/p97 promotes 53BP1 recruitment by removing L3MBTL1 from DNA double-strand breaks. Nat Struct Mol Biol. 2011;18:1345-50 pubmed publisher..The ATPase activity of VCP promotes the release of the Polycomb protein L3MBTL1 from chromatin, which also binds the H4K20me2 histone mark, thereby facilitating 53BP1 recruitment...
- Li H, Fischle W, Wang W, Duncan E, Liang L, Murakami Ishibe S, et al. Structural basis for lower lysine methylation state-specific readout by MBT repeats of L3MBTL1 and an engineered PHD finger. Mol Cell. 2007;28:677-91 pubmedHuman L3MBTL1, which contains three malignant brain tumor (MBT) repeats, binds monomethylated and dimethylated lysines, but not trimethylated lysines, in several histone sequence contexts...
- Fujita K, Nakamura Y, Oka T, Ito H, Tamura T, Tagawa K, et al. A functional deficiency of TERA/VCP/p97 contributes to impaired DNA repair in multiple polyglutamine diseases. Nat Commun. 2013;4:1816 pubmed publisher..Taken together, our results provide a novel common pathomechanism in multiple polyglutamine diseases that is mediated by DNA repair function of TERA/VCP/p97. ..
- Gursoy Yuzugullu O, Carman C, Price B. Spatially restricted loading of BRD2 at DNA double-strand breaks protects H4 acetylation domains and promotes DNA repair. Sci Rep. 2017;7:12921 pubmed publisher..This creates a spatially restricted H4Ac/BRD2 domain which reorganizes chromatin at DSBs, limits binding of the L3MBTL1 repressor and promotes 53BP1 binding, while limiting end-resection of DSBs...
- MacGrogan D, Kalakonda N, Alvarez S, Scandura J, Boccuni P, Johansson B, et al. Structural integrity and expression of the L3MBTL gene in normal and malignant hematopoietic cells. Genes Chromosomes Cancer. 2004;41:203-13 pubmedThe human L3MBTL gene is located in 20q12, a region that is commonly deleted in myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML)...
- Perna F, Vu L, Themeli M, Kriks S, Hoya Arias R, Khanin R, et al. The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells. Stem Cell Reports. 2015;4:658-69 pubmed publisher..We demonstrate that the Polycomb protein L3MBTL1, which is monoallelically deleted in 20q- myeloid malignancies, represses the ability of stem cells to drive ..
- Min J, Allali Hassani A, Nady N, Qi C, Ouyang H, Liu Y, et al. L3MBTL1 recognition of mono- and dimethylated histones. Nat Struct Mol Biol. 2007;14:1229-30 pubmedCrystal structures of the L3MBTL1 MBT repeats in complex with histone H4 peptides dimethylated on Lys20 (H4K20me2) show that only the second of the three MBT repeats can bind mono- and dimethylated histone peptides...
- Zeng H, Irwin M, Lu L, Risch H, Mayne S, Mu L, et al. Physical activity and breast cancer survival: an epigenetic link through reduced methylation of a tumor suppressor gene L3MBTL1. Breast Cancer Res Treat. 2012;133:127-35 pubmed publisher..e., higher expression associated with better survival. Of the three genes, L3MBTL1 was a putative tumor suppressor gene with known function to repress chromatin for transcription, which is ..
- Wang W, Tereshko V, Boccuni P, MacGrogan D, Nimer S, Patel D. Malignant brain tumor repeats: a three-leaved propeller architecture with ligand/peptide binding pockets. Structure. 2003;11:775-89 pubmed..Strikingly, phenotypic alterations resulting from point mutations or deletions in the mbt repeats of the related Drosophila SCM protein are clustered in and around the ligand binding pocket. ..
- Trojer P, Zhang J, Yonezawa M, Schmidt A, Zheng H, Jenuwein T, et al. Dynamic Histone H1 Isotype 4 Methylation and Demethylation by Histone Lysine Methyltransferase G9a/KMT1C and the Jumonji Domain-containing JMJD2/KDM4 Proteins. J Biol Chem. 2009;284:8395-405 pubmed publisher..in vitro and in vivo and thereby provides a recognition surface for the chromatin-binding proteins HP1 and L3MBTL1. Moreover, we show evidence that G9a promotes H1 deposition and is required for retention of H1 on chromatin...
- Perna F, Gurvich N, Hoya Arias R, Abdel Wahab O, Levine R, Asai T, et al. Depletion of L3MBTL1 promotes the erythroid differentiation of human hematopoietic progenitor cells: possible role in 20q- polycythemia vera. Blood. 2010;116:2812-21 pubmed publisherb>L3MBTL1, the human homolog of the Drosophila L(3)MBT polycomb group tumor suppressor gene, is located on chromosome 20q12, within the common deleted region identified in patients with 20q deletion-associated polycythemia vera, ..
- Gurvich N, Perna F, Farina A, Voza F, Menendez S, Hurwitz J, et al. L3MBTL1 polycomb protein, a candidate tumor suppressor in del(20q12) myeloid disorders, is essential for genome stability. Proc Natl Acad Sci U S A. 2010;107:22552-7 pubmed publisherThe l3mbtl1 gene is located on the long arm of chromosome 20 (q12), within a region commonly deleted in several myeloid malignancies...
- Fossey S, Mychaleckyj J, Pendleton J, Snyder J, Bensen J, Hirakawa S, et al. A high-resolution 6.0-megabase transcript map of the type 2 diabetes susceptibility region on human chromosome 20. Genomics. 2001;76:45-57 pubmed..The combination of the BAC transcript map, YAC-to-BAC scaffold, and reference Human Genome Project sequence provides a powerful integrated resource for future genomic analysis of this region. ..
- Li J, Bench A, Vassiliou G, Fourouclas N, Ferguson Smith A, Green A. Imprinting of the human L3MBTL gene, a polycomb family member located in a region of chromosome 20 deleted in human myeloid malignancies. Proc Natl Acad Sci U S A. 2004;101:7341-6 pubmedb>L3MBTL encodes a member of the Polycomb family of proteins, which, together with Trithorax group proteins, is responsible for the coordinated regulation of patterns of gene activity...
- Koga H, Matsui S, Hirota T, Takebayashi S, Okumura K, Saya H. A human homolog of Drosophila lethal(3)malignant brain tumor (l(3)mbt) protein associates with condensed mitotic chromosomes. Oncogene. 1999;18:3799-809 pubmed..These observations suggest that h-l(3)mbt protein has functions distinct from those of PcG proteins and may play a role in proper progression of cell division. ..
- Qi H, Sarkissian M, Hu G, Wang Z, Bhattacharjee A, Gordon D, et al. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature. 2010;466:503-7 pubmed publisher..Our findings indicate that an imbalance of histone methylation dynamics has a critical role in XLMR. ..