Kmt2a

Summary

Gene Symbol: Kmt2a
Description: lysine (K)-specific methyltransferase 2A
Alias: 6430520K01, ALL-1, All1, Cxxc7, HRX, HTRX1, Mll, Mll1, mKIAA4050, histone-lysine N-methyltransferase 2A, histone-lysine N-methyltransferase MLL, myeloid/lymphoid or mixed-lineage leukemia protein 1, trithorax Drosophila, zinc finger protein HRX
Species: mouse
Products:     Kmt2a

Top Publications

  1. Dobson C, Warren A, Pannell R, Forster A, Lavenir I, Corral J, et al. The mll-AF9 gene fusion in mice controls myeloproliferation and specifies acute myeloid leukaemogenesis. EMBO J. 1999;18:3564-74 pubmed
    The MLL gene from human chromosome 11q23 is involved in >30 different chromosomal translocations resulting in a plethora of different MLL fusion proteins...
  2. Gu Y, Nakamura T, Alder H, Prasad R, Canaani O, Cimino G, et al. The t(4;11) chromosome translocation of human acute leukemias fuses the ALL-1 gene, related to Drosophila trithorax, to the AF-4 gene. Cell. 1992;71:701-8 pubmed
    ..This suggests that each 11q23 abnormality gives rise to a specific oncogenic fusion protein. ..
  3. Yu B, Hess J, Horning S, Brown G, Korsmeyer S. Altered Hox expression and segmental identity in Mll-mutant mice. Nature. 1995;378:505-8 pubmed
    The mixed-lineage leukaemia gene (MLL/HRX/ALL-1) is disrupted by chromosomal translocation in human acute leukaemias that often display mixed lymphoid-myeloid phenotypes and present in infancy...
  4. Oyama T, Sasagawa S, Takeda S, Hess R, Lieberman P, Cheng E, et al. Cleavage of TFIIA by Taspase1 activates TRF2-specified mammalian male germ cell programs. Dev Cell. 2013;27:188-200 pubmed publisher
    ..Taspase1 is a protease that cleaves nuclear factors MLL1, MLL2, TFIIA?-?, and ALF?-? (TFIIA?)...
  5. Wang J, Iwasaki H, Krivtsov A, Febbo P, Thorner A, Ernst P, et al. Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease. EMBO J. 2005;24:368-81 pubmed
    Chromosomal translocations that fuse the mixed lineage leukemia (MLL) gene with multiple partners typify acute leukemias of infancy as well as therapy-related leukemias...
  6. Milne T, Briggs S, Brock H, Martin M, Gibbs D, Allis C, et al. MLL targets SET domain methyltransferase activity to Hox gene promoters. Mol Cell. 2002;10:1107-17 pubmed
    b>MLL, the human homolog of Drosophila trithorax, maintains Hox gene expression in mammalian embryos and is rearranged in human leukemias resulting in Hox gene deregulation...
  7. Takeda S, Chen D, Westergard T, Fisher J, Rubens J, Sasagawa S, et al. Proteolysis of MLL family proteins is essential for taspase1-orchestrated cell cycle progression. Genes Dev. 2006;20:2397-409 pubmed
    Taspase1 was identified as the threonine endopeptidase that cleaves mixed-lineage leukemia (MLL) for proper Hox gene expression in vitro. To investigate its functions in vivo, we generated Taspase1(-/-) mice...
  8. Daser A, Rabbitts T. Extending the repertoire of the mixed-lineage leukemia gene MLL in leukemogenesis. Genes Dev. 2004;18:965-74 pubmed
  9. Ernst P, Fisher J, Avery W, Wade S, Foy D, Korsmeyer S. Definitive hematopoiesis requires the mixed-lineage leukemia gene. Dev Cell. 2004;6:437-43 pubmed
    The Mixed-Lineage Leukemia (MLL) gene encodes a Trithorax-related chromatin-modifying protooncogene that positively regulates Hox genes...

More Information

Publications83

  1. Ayton P, Sneddon S, Palmer D, Rosewell I, Owen M, Young B, et al. Truncation of the Mll gene in exon 5 by gene targeting leads to early preimplantation lethality of homozygous embryos. Genesis. 2001;30:201-12 pubmed
    The mixed lineage leukemia gene (MLL) was originally identified through its involvement in reciprocal translocations in leukemias...
  2. Liu H, Takeda S, Kumar R, Westergard T, Brown E, Pandita T, et al. Phosphorylation of MLL by ATR is required for execution of mammalian S-phase checkpoint. Nature. 2010;467:343-6 pubmed publisher
    ..Reconstitution of Mll(-/-) (Mll also known as Mll1) mouse embryonic fibroblasts with wild-type but not S516A or ?SET mutant MLL rescues the S-phase checkpoint defects...
  3. Gan T, Jude C, Zaffuto K, Ernst P. Developmentally induced Mll1 loss reveals defects in postnatal haematopoiesis. Leukemia. 2010;24:1732-41 pubmed publisher
    The mixed lineage leukemia (MLL) gene is disrupted by chromosomal translocations in acute leukemia, producing a fusion oncogene with altered properties relative to the wild-type gene...
  4. Zeisig B, Garcia Cuellar M, Winkler T, Slany R. The oncoprotein MLL-ENL disturbs hematopoietic lineage determination and transforms a biphenotypic lymphoid/myeloid cell. Oncogene. 2003;22:1629-37 pubmed
    Mixed-lineage leukemia (MLL) fusion proteins are associated with a unique class of leukemia that is characterized by the simultaneous expression of lymphoid-specific as well as myeloid-specific genes...
  5. Thiel A, Blessington P, Zou T, Feather D, Wu X, Yan J, et al. MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele. Cancer Cell. 2010;17:148-59 pubmed publisher
    ..The mixed lineage leukemia (MLL) gene undergoes chromosomal translocations, resulting in the formation of oncogenic MLL fusion proteins (MLL-FPs)...
  6. Krivtsov A, Feng Z, Lemieux M, Faber J, Vempati S, Sinha A, et al. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell. 2008;14:355-68 pubmed publisher
    We created a mouse model wherein conditional expression of an Mll-AF4 fusion oncogene induces B precursor acute lymphoblastic (ALL) or acute myeloid leukemias (AML)...
  7. Jude C, Climer L, Xu D, Artinger E, Fisher J, Ernst P. Unique and independent roles for MLL in adult hematopoietic stem cells and progenitors. Cell Stem Cell. 2007;1:324-37 pubmed publisher
    The Mixed Lineage Leukemia (MLL) gene is essential for embryonic hematopoietic stem cell (HSC) development, but its role during adult hematopoiesis is unknown...
  8. Yagi H, Deguchi K, Aono A, Tani Y, Kishimoto T, Komori T. Growth disturbance in fetal liver hematopoiesis of Mll-mutant mice. Blood. 1998;92:108-17 pubmed
    The MLL (ALL-1, HRX) gene is frequently involved in chromosomal translocations in acute leukemia and has homology with Drosophila trithorax, which controls homeobox gene expression and embryogenesis...
  9. Milne T, Hughes C, Lloyd R, Yang Z, Rozenblatt Rosen O, Dou Y, et al. Menin and MLL cooperatively regulate expression of cyclin-dependent kinase inhibitors. Proc Natl Acad Sci U S A. 2005;102:749-54 pubmed
    ..We have recently shown that menin, the MEN1 protein product, interacts with mixed lineage leukemia (MLL) family proteins in a histone methyltransferase complex including Ash2, Rbbp5, and WDR5...
  10. Kumar A, Hudson W, Chen W, Nishiuchi R, Yao Q, Kersey J. Hoxa9 influences the phenotype but not the incidence of Mll-AF9 fusion gene leukemia. Blood. 2004;103:1823-8 pubmed
    Identification of the targets of mixed lineage leukemia (MLL) fusion genes will assist in understanding the biology of MLL fusion gene leukemias and in development of better therapies...
  11. Artinger E, Mishra B, Zaffuto K, Li B, Chung E, Moore A, et al. An MLL-dependent network sustains hematopoiesis. Proc Natl Acad Sci U S A. 2013;110:12000-5 pubmed publisher
    The histone methyltransferase Mixed Lineage Leukemia (MLL) is essential to maintain hematopoietic stem cells and is a leukemia protooncogene...
  12. Li B, Gan T, Meyerson M, Rabbitts T, Ernst P. Distinct pathways regulated by menin and by MLL1 in hematopoietic stem cells and developing B cells. Blood. 2013;122:2039-46 pubmed publisher
    Mixed Lineage Leukemia (MLL1) translocations encode fusion proteins retaining the N terminus of MLL1, which interacts with the tumor suppressor, menin. This interaction is essential for leukemogenesis and thus is a promising drug target...
  13. Yokoyama A, Ficara F, Murphy M, Meisel C, Hatanaka C, Kitabayashi I, et al. MLL becomes functional through intra-molecular interaction not by proteolytic processing. PLoS ONE. 2013;8:e73649 pubmed publisher
    The mixed lineage leukemia (MLL) protein is an epigenetic transcriptional regulator that controls proliferative expansion of immature hematopoietic progenitors, whose aberrant activation triggers leukemogenesis...
  14. Milne T, Kim J, Wang G, Stadler S, Basrur V, Whitcomb S, et al. Multiple interactions recruit MLL1 and MLL1 fusion proteins to the HOXA9 locus in leukemogenesis. Mol Cell. 2010;38:853-63 pubmed publisher
    b>MLL1 fusion proteins activate HoxA9 gene expression and cause aggressive leukemias that respond poorly to treatment, but how they recognize and stably bind to HoxA9 is not clearly understood...
  15. Dobson C, Warren A, Pannell R, Forster A, Rabbitts T. Tumorigenesis in mice with a fusion of the leukaemia oncogene Mll and the bacterial lacZ gene. EMBO J. 2000;19:843-51 pubmed
    ..Molecular analyses revealed that the MLL gene (also called ALL-1, HRX or HTRX) is broken by the translocations, causing fusion with genes from other chromosomes...
  16. Corral J, Lavenir I, Impey H, Warren A, Forster A, Larson T, et al. An Mll-AF9 fusion gene made by homologous recombination causes acute leukemia in chimeric mice: a method to create fusion oncogenes. Cell. 1996;85:853-61 pubmed
    ..AF9 sequences were fused into the mouse Mll gene so that expression of the Mll-AF9 fusion gene occurred from endogenous Mll transcription control elements, as ..
  17. Yu B, Hanson R, Hess J, Horning S, Korsmeyer S. MLL, a mammalian trithorax-group gene, functions as a transcriptional maintenance factor in morphogenesis. Proc Natl Acad Sci U S A. 1998;95:10632-6 pubmed
    ..We have examined the developmental role of a mammalian homolog of trx and putative oncogene, Mll. Knockout mice reveal that Mll is required for maintenance of gene expression early in embryogenesis...
  18. McMahon K, Hiew S, Hadjur S, Veiga Fernandes H, Menzel U, Price A, et al. Mll has a critical role in fetal and adult hematopoietic stem cell self-renewal. Cell Stem Cell. 2007;1:338-45 pubmed publisher
    The Mixed Lineage Leukemia (Mll) gene is a homolog of Drosophila Trithorax commonly rearranged in infant leukemia...
  19. Terranova R, Agherbi H, Boned A, Méresse S, Djabali M. Histone and DNA methylation defects at Hox genes in mice expressing a SET domain-truncated form of Mll. Proc Natl Acad Sci U S A. 2006;103:6629-34 pubmed
    The Mll gene is a member of the mammalian trithorax group, involved with the antagonistic Polycomb group in epigenetic regulation of homeotic genes. MLL contains a highly conserved SET domain also found in various chromatin proteins...
  20. Tkachuk D, Kohler S, Cleary M. Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell. 1992;71:691-700 pubmed
    ..Human trithorax (HRX) is a predicted 431 kd protein containing two potential DNA-binding motifs consisting of zinc fingers conserved ..
  21. Hsieh J, Cheng E, Korsmeyer S. Taspase1: a threonine aspartase required for cleavage of MLL and proper HOX gene expression. Cell. 2003;115:293-303 pubmed
    The Mixed-Lineage Leukemia gene (MLL/HRX/ALL1) encodes a large nuclear protein homologous to Drosophila trithorax that is required for the maintenance of HOX gene expression...
  22. Ayton P, Chen E, Cleary M. Binding to nonmethylated CpG DNA is essential for target recognition, transactivation, and myeloid transformation by an MLL oncoprotein. Mol Cell Biol. 2004;24:10470-8 pubmed
    The MLL gene is a frequent target for leukemia-associated chromosomal translocations that generate dominant-acting chimeric oncoproteins...
  23. Takeda S, Liu H, Sasagawa S, Dong Y, Trainor P, Cheng E, et al. HGF-MET signals via the MLL-ETS2 complex in hepatocellular carcinoma. J Clin Invest. 2013;123:3154-65 pubmed publisher
    ..Mixed-lineage leukemia (MLL), an epigenetic regulator, plays critical roles in cell fate, stem cell, and cell cycle decisions...
  24. Yokoyama A, Ficara F, Murphy M, Meisel C, Naresh A, Kitabayashi I, et al. Proteolytically cleaved MLL subunits are susceptible to distinct degradation pathways. J Cell Sci. 2011;124:2208-19 pubmed publisher
    The mixed lineage leukemia (MLL) proto-oncogenic protein is a histone-lysine N-methyltransferase that is produced by proteolytic cleavage and self-association of the respective functionally distinct subunits (MLL(N) and MLL(C)) to form a ..
  25. Smith L, Yeung J, Zeisig B, Popov N, Huijbers I, Barnes J, et al. Functional crosstalk between Bmi1 and MLL/Hoxa9 axis in establishment of normal hematopoietic and leukemic stem cells. Cell Stem Cell. 2011;8:649-62 pubmed publisher
    ..AML1-ETO and PLZF-RAR?, which do not activate Hox, triggered senescence in Bmi1(-/-) cells. In contrast, MLL-AF9, which drives expression of Hoxa7 and Hoxa9, readily transformed Bmi1(-/-) cells...
  26. Li B, Ernst P. Two decades of leukemia oncoprotein epistasis: the MLL1 paradigm for epigenetic deregulation in leukemia. Exp Hematol. 2014;42:995-1012 pubmed publisher
    b>MLL1, located on human chromosome 11, is disrupted in distinct recurrent chromosomal translocations in several leukemia subsets...
  27. Walf Vorderwülbecke V, de Boer J, Horton S, van Amerongen R, Proost N, Berns A, et al. Frat2 mediates the oncogenic activation of Rac by MLL fusions. Blood. 2012;120:4819-28 pubmed publisher
    Mixed lineage leukemia (MLL) fusion genes arise from chromosomal translocations and induce acute myeloid leukemia through a mechanism involving transcriptional deregulation of differentiation and self-renewal programs...
  28. Kawabe Y, Wang Y, McKinnell I, Bedford M, Rudnicki M. Carm1 regulates Pax7 transcriptional activity through MLL1/2 recruitment during asymmetric satellite stem cell divisions. Cell Stem Cell. 2012;11:333-45 pubmed publisher
    ..Methylated Pax7 directly binds the C-terminal cleavage forms of the trithorax proteins MLL1/2 resulting in the recruitment of the ASH2L:MLL1/2:WDR5:RBBP5 histone H3K4 methyltransferase complex to regulatory ..
  29. Takacova S, Slany R, Bartkova J, Stránecký V, Dolezel P, Luzna P, et al. DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo. Cancer Cell. 2012;21:517-31 pubmed publisher
    Activation of the MLL-ENL-ERtm oncogene initiates aberrant proliferation of myeloid progenitors...
  30. Nanya M, Sato M, Tanimoto K, Tozuka M, Mizutani S, Takagi M. Dysregulation of the DNA Damage Response and KMT2A Rearrangement in Fetal Liver Hematopoietic Cells. PLoS ONE. 2015;10:e0144540 pubmed publisher
    Etoposide, a topoisomerase 2 (TOP2) inhibitor, is associated with the development of KMT2A (MLL)-rearranged infant leukemia...
  31. Carson W, Cavassani K, Soares E, Hirai S, Kittan N, Schaller M, et al. The STAT4/MLL1 Epigenetic Axis Regulates the Antimicrobial Functions of Murine Macrophages. J Immunol. 2017;199:1865-1874 pubmed publisher
    ..The histone methyltransferase mixed-lineage leukemia 1 (MLL1) preferentially modifies lysine residue 4 on the unstructured protein tail of histone H3...
  32. Mi S, Li Z, Chen P, He C, Cao D, Elkahloun A, et al. Aberrant overexpression and function of the miR-17-92 cluster in MLL-rearranged acute leukemia. Proc Natl Acad Sci U S A. 2010;107:3710-5 pubmed publisher
    ..found that it is also frequently amplified and the miRNAs are aberrantly overexpressed in mixed lineage leukemia (MLL)-rearranged acute leukemias...
  33. Kim W, Matise I, Diers M, Largaespada D. RAS oncogene suppression induces apoptosis followed by more differentiated and less myelosuppressive disease upon relapse of acute myeloid leukemia. Blood. 2009;113:1086-96 pubmed publisher
    ..we used a Vav promoter-tetracycline transactivator (Vav-tTA)-driven repressible TRE-NRAS(G12V) transgene system in Mll-AF9 knock-in mice developing AML...
  34. Huang H, Matevossian A, Whittle C, Kim S, Schumacher A, Baker S, et al. Prefrontal dysfunction in schizophrenia involves mixed-lineage leukemia 1-regulated histone methylation at GABAergic gene promoters. J Neurosci. 2007;27:11254-62 pubmed
    ..Heterozygosity for a truncated, lacZ knock-in allele of mixed-lineage leukemia 1 (Mll1), a histone methyltransferase expressed in GABAergic and other cortical neurons, resulted in decreased H3K4 ..
  35. Hanson R, Hess J, Yu B, Ernst P, van Lohuizen M, Berns A, et al. Mammalian Trithorax and polycomb-group homologues are antagonistic regulators of homeotic development. Proc Natl Acad Sci U S A. 1999;96:14372-7 pubmed
    ..Mixed lineage leukemia (MLL) is frequently involved in chromosomal translocations associated with acute leukemia and is the one established ..
  36. Kimball A, Joshi A, Carson W, Boniakowski A, Schaller M, ALLEN R, et al. The Histone Methyltransferase MLL1 Directs Macrophage-Mediated Inflammation in Wound Healing and Is Altered in a Murine Model of Obesity and Type 2 Diabetes. Diabetes. 2017;66:2459-2471 pubmed publisher
    ..Mixed-lineage leukemia-1 (MLL1) has been shown to direct gene expression by regulating nuclear factor-?B (NF-?B)-mediated inflammatory gene ..
  37. Jones M, Chase J, Brinkmeier M, Xu J, Weinberg D, Schira J, et al. Ash1l controls quiescence and self-renewal potential in hematopoietic stem cells. J Clin Invest. 2015;125:2007-20 pubmed publisher
    ..Ash1l cooperated functionally with mixed-lineage leukemia 1 (Mll1), as combined loss of Ash1l and Mll1, but not isolated Ash1l or Mll1 deficiency, induced overt hematopoietic ..
  38. Deshpande A, Chen L, Fazio M, Sinha A, Bernt K, Banka D, et al. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l. Blood. 2013;121:2533-41 pubmed publisher
    ..In this study, we demonstrate that MLL-AF6 requires continued activity of the histone-methyltransferase DOT1L to maintain expression of the MLL-AF6-driven ..
  39. Hu T, Li C, Zhang Y, Wang L, Peng L, Cheng H, et al. Phosphoinositide-dependent kinase 1 regulates leukemia stem cell maintenance in MLL-AF9-induced murine acute myeloid leukemia. Biochem Biophys Res Commun. 2015;459:692-8 pubmed publisher
    ..However, the role of PDK1 in the regulation of LSCs in AML is still not clear. Using a PDK1 conditional deletion MLL-AF9 murine AML model, we revealed that the deletion of PDK1 prolonged the survival of AML mice by inducing LSC ..
  40. Schaller M, Ito T, Allen R, Kroetz D, Kittan N, Ptaschinski C, et al. Epigenetic regulation of IL-12-dependent T cell proliferation. J Leukoc Biol. 2015;98:601-13 pubmed publisher
    ..We here demonstrated that the expression of the histone methyltransferase Mll1 is driven by IL-12 signaling through STAT4 in humans and mice and is critical for the proper differentiation of a ..
  41. Dorrance A, Liu S, Chong A, Pulley B, Nemer D, Guimond M, et al. The Mll partial tandem duplication: differential, tissue-specific activity in the presence or absence of the wild-type allele. Blood. 2008;112:2508-11 pubmed publisher
    The partial tandem duplication of MLL (MLL-PTD) is found in 5% to 10% of patients with acute myeloid leukemia (AML) and normal cytogenetics. Its expression in leukemic blasts is coincident with a silenced wild-type (WT) MLL allele...
  42. Muntean A, Giannola D, Udager A, Hess J. The PHD fingers of MLL block MLL fusion protein-mediated transformation. Blood. 2008;112:4690-3 pubmed publisher
    Chromosomal translocations involving the mixed lineage leukemia (MLL) gene are associated with aggressive acute lymphoid and myeloid leukemias. These translocations are restricted to an 8...
  43. So C, Karsunky H, Wong P, Weissman I, Cleary M. Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of Hoxa7 or Hoxa9. Blood. 2004;103:3192-9 pubmed
    ..of Hox gene expression, particularly Hoxa7 and Hoxa9, is a feature of leukemias harboring mixed-lineage leukemia (MLL) mutations...
  44. Artinger E, Ernst P. Cell context in the control of self-renewal and proliferation regulated by MLL1. Cell Cycle. 2013;12:2969-72 pubmed publisher
    Mixed lineage leukemia 1 (MLL1) is a gene that is disrupted by chromosomal translocation characteristically in a large proportion of infant leukemia and also in a fraction of childhood and adult leukemia...
  45. Shen E, Jiang Y, Javidfar B, Kassim B, Loh Y, Ma Q, et al. Neuronal Deletion of Kmt2a/Mll1 Histone Methyltransferase in Ventral Striatum is Associated with Defective Spike-Timing-Dependent Striatal Synaptic Plasticity, Altered Response to Dopaminergic Drugs, and Increased Anxiety. Neuropsychopharmacology. 2016;41:3103-3113 pubmed publisher
    Lysine (K) methyltransferase 2a (Kmt2a) and other regulators of H3 lysine 4 methylation, a histone modification enriched at promoters and enhancers, are widely expressed throughout the brain, but molecular and cellular phenotypes in ..
  46. Zhang Y, Yan X, Sashida G, Zhao X, Rao Y, Goyama S, et al. Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells. Blood. 2012;120:1118-29 pubmed publisher
    One mechanism for disrupting the MLL gene in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is through partial tandem duplication (MLL-PTD); however, the mechanism by which MLL-PTD contributes to MDS and AML development ..
  47. Chen W, O Sullivan M, Hudson W, Kersey J. Modeling human infant MLL leukemia in mice: leukemia from fetal liver differs from that originating in postnatal marrow. Blood. 2011;117:3474-5 pubmed publisher
  48. Katada S, Sassone Corsi P. The histone methyltransferase MLL1 permits the oscillation of circadian gene expression. Nat Struct Mol Biol. 2010;17:1414-21 pubmed publisher
    ..b>MLL1, a mammalian homolog of Drosophila trithorax, is an H3K4-specific methyltransferase implicated in transcriptional ..
  49. Morgado Palacin I, Day A, Murga M, Lafarga V, Anton M, Tubbs A, et al. Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML. Sci Signal. 2016;9:ra91 pubmed publisher
    Among the various subtypes of acute myeloid leukemia (AML), those with chromosomal rearrangements of the MLL oncogene (AML-MLL) have a poor prognosis...
  50. Wang X, Chen C, Armstrong S. The role of DOT1L in the maintenance of leukemia gene expression. Curr Opin Genet Dev. 2016;36:68-72 pubmed publisher
    ..Mouse modeling suggests the methyltransferase DOT1L as a potential therapeutic target for MLL-rearranged leukemia...
  51. Riedel S, Haladyna J, Bezzant M, Stevens B, Pollyea D, Sinha A, et al. MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia. J Clin Invest. 2016;126:1438-50 pubmed publisher
    ..Here, we have shown that this program is controlled by two histone methyltransferases, MLL1 and DOT1L, as deletion of either Mll1 or Dot1l in MN1-expressing cells abrogated the cell of origin-derived gene ..
  52. Popovic R, Riesbeck L, Velu C, Chaubey A, Zhang J, Achille N, et al. Regulation of mir-196b by MLL and its overexpression by MLL fusions contributes to immortalization. Blood. 2009;113:3314-22 pubmed publisher
    Chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene produce chimeric proteins that cause abnormal expression of a subset of HOX genes and leukemia development...
  53. Huang G, Zhao X, Wang L, Elf S, Xu H, Zhao X, et al. The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood. 2011;118:6544-52 pubmed publisher
    The mixed-lineage leukemia (MLL) H3K4 methyltransferase protein, and the heterodimeric RUNX1/CBF? transcription factor complex, are critical for definitive and adult hematopoiesis, and both are frequently targeted in human acute leukemia...
  54. Muntean A, Chen W, Jones M, Granowicz E, Maillard I, Hess J. MLL fusion protein-driven AML is selectively inhibited by targeted disruption of the MLL-PAFc interaction. Blood. 2013;122:1914-22 pubmed publisher
    b>MLL rearrangements are common in leukemia and considered an adverse risk factor...
  55. Gao Y, Gao J, Li M, Zheng Y, Wang Y, Zhang H, et al. Rheb1 promotes tumor progression through mTORC1 in MLL-AF9-initiated murine acute myeloid leukemia. J Hematol Oncol. 2016;9:36 pubmed publisher
    ..Using a Rheb1-deficient MLL-AF9 murine AML model, we revealed that Rheb1 deletion prolonged the survival of AML mice by weakening LSC function...
  56. Cano F, Drynan L, Pannell R, Rabbitts T. Leukaemia lineage specification caused by cell-specific Mll-Enl translocations. Oncogene. 2008;27:1945-50 pubmed
    Chromosomal translocations involving the Mixed-Lineage Leukaemia (MLL) gene underlie many human leukaemias and MLL rearrangements are found in both acute myelogenous and acute lymphoblastic leukaemias...
  57. Yang Z, Augustin J, Hu J, Jiang H. Physical Interactions and Functional Coordination between the Core Subunits of Set1/Mll Complexes and the Reprogramming Factors. PLoS ONE. 2015;10:e0145336 pubmed publisher
    ..Oct4, Sox2, Klf4 and Myc), especially Myc, directly promotes the expression of certain core subunits of the Set1/Mll family of H3K4 methyltransferase complexes...
  58. Chen W, Kumar A, Hudson W, Li Q, Wu B, Staggs R, et al. Malignant transformation initiated by Mll-AF9: gene dosage and critical target cells. Cancer Cell. 2008;13:432-40 pubmed publisher
    The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined...
  59. Wang P, Lin C, Smith E, Guo H, Sanderson B, Wu M, et al. Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II. Mol Cell Biol. 2009;29:6074-85 pubmed publisher
    ..H3K4 methylase in Saccharomyces cerevisiae; however, in mammals, at least six H3K4 methylases, Set1A and Set1B and MLL1 to MLL4, are found in COMPASS-like complexes capable of methylating H3K4...
  60. Chen Y, Anastassiadis K, Kranz A, Stewart A, Arndt K, Waskow C, et al. MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia. Cancer Cell. 2017;31:755-770.e6 pubmed publisher
    The MLL1 histone methyltransferase gene undergoes many distinct chromosomal rearrangements to yield poor-prognosis leukemia. The remaining wild-type allele is most commonly, but not always, retained...
  61. Kranz A, Fu J, Duerschke K, Weidlich S, Naumann R, Stewart A, et al. An improved Flp deleter mouse in C57Bl/6 based on Flpo recombinase. Genesis. 2010;48:512-20 pubmed publisher
    ..In breeding experiments, we show that the Flpo deleter delivers complete recombination using alleles that are incompletely recombined by a commonly used Flpe deleter. This indicates that the Flpo deleter is more efficient. ..
  62. Zhang H, Gayen S, Xiong J, Zhou B, Shanmugam A, Sun Y, et al. MLL1 Inhibition Reprograms Epiblast Stem Cells to Naive Pluripotency. Cell Stem Cell. 2016;18:481-94 pubmed publisher
    ..Here, we show that blocking histone H3K4 methyltransferase MLL1 activity with the small-molecule inhibitor MM-401 reprograms mouse epiblast stem cells (EpiSCs) to naive ..
  63. Yamashita M, Hirahara K, Shinnakasu R, Hosokawa H, Norikane S, Kimura M, et al. Crucial role of MLL for the maintenance of memory T helper type 2 cell responses. Immunity. 2006;24:611-22 pubmed
    The Mixed-Lineage Leukemia (MLL) gene, a mammalian homolog of the Drosophila trithorax, is implicated in regulating the maintenance of Hox gene expression and hematopoiesis...
  64. Deng C, Li Y, Zhou L, Cho J, Patel B, Terada N, et al. HoxBlinc RNA Recruits Set1/MLL Complexes to Activate Hox Gene Expression Patterns and Mesoderm Lineage Development. Cell Rep. 2016;14:103-114 pubmed publisher
    ..HoxBlinc binds to the hoxb genes, recruits Setd1a/MLL1 complexes, and mediates long-range chromatin interactions to activate transcription of the hoxb genes...
  65. Biswas D, Milne T, Basrur V, Kim J, Elenitoba Johnson K, Allis C, et al. Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through distinct partner protein complexes. Proc Natl Acad Sci U S A. 2011;108:15751-6 pubmed publisher
    A number of acute leukemias arise from fusion of the mixed lineage leukemia 1 protein (MLL) N terminus to a variety of fusion partners that have been reported to reside in one or more poorly defined complexes linked to transcription ..
  66. Collins E, Pannell R, Simpson E, Forster A, Rabbitts T. Inter-chromosomal recombination of Mll and Af9 genes mediated by cre-loxP in mouse development. EMBO Rep. 2000;1:127-32 pubmed
    ..We have used the Cre-loxP system of phage P1 to induce de novo Mll-Af9 chromosomal recombination during mouse development...
  67. Gupta S, Kim S, Artis S, Molfese D, Schumacher A, Sweatt J, et al. Histone methylation regulates memory formation. J Neurosci. 2010;30:3589-99 pubmed publisher
    ..We also found that mice deficient in the H3K4-specific histone methyltransferase, Mll, displayed deficits in contextual fear conditioning relative to wild-type animals...
  68. Tamai H, Yamaguchi H, Miyake K, Takatori M, Kitano T, Yamanaka S, et al. Amlexanox Downregulates S100A6 to Sensitize KMT2A/AFF1-Positive Acute Lymphoblastic Leukemia to TNFα Treatment. Cancer Res. 2017;77:4426-4433 pubmed publisher
    Acute lymphoblastic leukemias (ALL) positive for KMT2A/AFF1 (MLL/AF4) translocation, which constitute 60% of all infant ALL cases, have a poor prognosis even after allogeneic hematopoietic stem cell transplantation (allo-..
  69. Kerimoglu C, Sakib M, Jain G, Benito E, Burkhardt S, Capece V, et al. KMT2A and KMT2B Mediate Memory Function by Affecting Distinct Genomic Regions. Cell Rep. 2017;20:538-548 pubmed publisher
    b>Kmt2a and Kmt2b are H3K4 methyltransferases of the Set1/Trithorax class. We have recently shown the importance of Kmt2b for learning and memory. Here, we report that Kmt2a is also important in memory formation...
  70. Wang X, Ju L, Fan J, Zhu Y, Liu X, Zhu K, et al. Histone H3K4 methyltransferase Mll1 regulates protein glycosylation and tunicamycin-induced apoptosis through transcriptional regulation. Biochim Biophys Acta. 2014;1843:2592-602 pubmed publisher
    ..A key function of the UPR is to restore ER homeostasis, but prolonged or unsolved ER stress can lead to apoptosis. MLL1 (Mixed Lineage Leukemia 1, also named ALL-1 or HRX), a histone H3K4 methyltransferase in mammals, plays important ..
  71. Jo S, Granowicz E, Maillard I, Thomas D, Hess J. Requirement for Dot1l in murine postnatal hematopoiesis and leukemogenesis by MLL translocation. Blood. 2011;117:4759-68 pubmed publisher
    ..DOT1L also interacts with translocation partners of Mixed Lineage Leukemia (MLL) gene, which is commonly translocated in human leukemia...
  72. Kaikkonen M, Spann N, Heinz S, Romanoski C, Allison K, Stender J, et al. Remodeling of the enhancer landscape during macrophage activation is coupled to enhancer transcription. Mol Cell. 2013;51:310-25 pubmed publisher
    ..H3K4 methylation at de novo enhancers is primarily dependent on the histone methyltransferases Mll1, Mll2/4, and Mll3 and is significantly reduced by inhibition of RNA polymerase II elongation...
  73. So C, Cleary M. MLL-AFX requires the transcriptional effector domains of AFX to transform myeloid progenitors and transdominantly interfere with forkhead protein function. Mol Cell Biol. 2002;22:6542-52 pubmed
    b>MLL-AFX is a fusion gene created by t(X;11) chromosomal translocations in a subset of acute leukemias of either myeloid or lymphoid derivation...
  74. Dorrance A, Liu S, Yuan W, Becknell B, Arnoczky K, Guimond M, et al. Mll partial tandem duplication induces aberrant Hox expression in vivo via specific epigenetic alterations. J Clin Invest. 2006;116:2707-16 pubmed
    We previously identified a rearrangement of mixed-lineage leukemia (MLL) gene (also known as ALL-1, HRX, and HTRX1), consisting of an in-frame partial tandem duplication (PTD) of exons 5 through 11 in the absence of a partner gene, ..