KMT2A

Summary

Gene Symbol: KMT2A
Description: lysine methyltransferase 2A
Alias: ALL-1, CXXC7, HRX, HTRX1, MLL, MLL1, MLL1A, TRX1, WDSTS, histone-lysine N-methyltransferase 2A, CXXC-type zinc finger protein 7, lysine (K)-specific methyltransferase 2A, lysine N-methyltransferase 2A, mixed lineage leukemia 1, myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila), trithorax-like protein, zinc finger protein HRX
Species: human
Products:     KMT2A

Top Publications

  1. Butler L, Slany R, Cui X, Cleary M, Mason D. The HRX proto-oncogene product is widely expressed in human tissues and localizes to nuclear structures. Blood. 1997;89:3361-70 pubmed
    Chromosomal rearrangement of the HRX (MLL, ALL-1, Htrx) gene situated at chromosome band 11q23 is one of the most frequent genetic changes in infant leukemias of myeloid and lymphoid lineage and in treatment-induced secondary leukemias...
  2. Ansari K, Kasiri S, Mandal S. Histone methylase MLL1 has critical roles in tumor growth and angiogenesis and its knockdown suppresses tumor growth in vivo. Oncogene. 2013;32:3359-70 pubmed publisher
    ..Herein, we demonstrated that antisense-mediated knockdown of MLL1 induced cell-cycle arrest and apoptosis in cultured cells...
  3. Milne T, Dou Y, Martin M, Brock H, Roeder R, Hess J. MLL associates specifically with a subset of transcriptionally active target genes. Proc Natl Acad Sci U S A. 2005;102:14765-70 pubmed
    b>MLL (mixed-lineage leukemia) is a histone H3 Lys-4 specific methyltransferase that is a positive regulator of Hox expression...
  4. 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...
  5. Meyer C, Kowarz E, Hofmann J, Renneville A, Zuna J, Trka J, et al. New insights to the MLL recombinome of acute leukemias. Leukemia. 2009;23:1490-9 pubmed publisher
    Chromosomal rearrangements of the human MLL gene are associated with high-risk pediatric, adult and therapy-associated acute leukemias...
  6. Diehl F, Rossig L, Zeiher A, Dimmeler S, Urbich C. The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation. Blood. 2007;109:1472-8 pubmed
    ..Here, we investigated the role of the histone lysine methyltransferase MLL for angiogenic functions in human umbilical vein endothelial cells...
  7. Liu H, Cheng E, Hsieh J. MLL fusions: pathways to leukemia. Cancer Biol Ther. 2009;8:1204-11 pubmed
    Human leukemias with chromosomal band 11q23 aberrations that disrupt the MLL/HRX/ALL-1 gene portend poor prognosis...
  8. Patel A, Vought V, Dharmarajan V, Cosgrove M. A novel non-SET domain multi-subunit methyltransferase required for sequential nucleosomal histone H3 methylation by the mixed lineage leukemia protein-1 (MLL1) core complex. J Biol Chem. 2011;286:3359-69 pubmed publisher
    ..activity requires a complex that includes WRAD (WDR5, RbBP5, Ash2L, and DPY-30), a complex that is part of the MLL1 (mixed lineage leukemia protein-1) core complex but that also exists independently of MLL1 in the cell...
  9. 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...

More Information

Publications81

  1. Kumar A, Yao Q, Li Q, Sam T, Kersey J. t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL. Leuk Res. 2011;35:305-9 pubmed publisher
    The most frequent MLL-gene rearrangement found in leukemia is a reciprocal translocation with AF4 on chromosome 4 resulting in the formation of the MLL-AF4 and the AF4-MLL fusion genes...
  2. Matsushita H, Nakajima H, Nakamura Y, Tsukamoto H, Tanaka Y, Jin G, et al. C/EBPalpha and C/EBPvarepsilon induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene. Oncogene. 2008;27:6749-60 pubmed publisher
    ..Therefore, the expression and function of C/EBPs in myelomonocytic cells with MLL-fusion genes were investigated...
  3. Avdic V, Zhang P, Lanouette S, Groulx A, Tremblay V, Brunzelle J, et al. Structural and biochemical insights into MLL1 core complex assembly. Structure. 2011;19:101-8 pubmed publisher
    ..The crystal structure of WDR5 in ternary complex with RbBP5 and MLL1 reveals that both proteins binds peptide-binding clefts located on opposite sides of WDR5's ?-propeller domain...
  4. Jones W, Dafou D, McEntagart M, Woollard W, Elmslie F, Holder Espinasse M, et al. De novo mutations in MLL cause Wiedemann-Steiner syndrome. Am J Hum Genet. 2012;91:358-64 pubmed publisher
    ..Utilizing a whole-exome sequencing approach, we identified de novo mutations in MLL in five of the six individuals...
  5. Tan J, Jones M, Koseki H, Nakayama M, Muntean A, Maillard I, et al. CBX8, a polycomb group protein, is essential for MLL-AF9-induced leukemogenesis. Cancer Cell. 2011;20:563-75 pubmed publisher
    Chromosomal translocations involving the mixed lineage leukemia (MLL) gene lead to the development of acute leukemias...
  6. Chen J, Santillan D, Koonce M, Wei W, Luo R, Thirman M, et al. Loss of MLL PHD finger 3 is necessary for MLL-ENL-induced hematopoietic stem cell immortalization. Cancer Res. 2008;68:6199-207 pubmed publisher
    Reciprocal chromosomal translocations at the MLL gene locus result in expression of novel fusion proteins, such as MLL-ENL, associated with leukemia...
  7. Rozovskaia T, Rozenblatt Rosen O, Sedkov Y, Burakov D, Yano T, Nakamura T, et al. Self-association of the SET domains of human ALL-1 and of Drosophila TRITHORAX and ASH1 proteins. Oncogene. 2000;19:351-7 pubmed
    ..SET-SET interactions might act in integrating the activity of ALL-1 (TRX and ASH1) protein molecules, simultaneously positioned at different maintenance elements and directing expression of the same or different target genes. ..
  8. Dharmarajan V, Lee J, Patel A, Skalnik D, Cosgrove M. Structural basis for WDR5 interaction (Win) motif recognition in human SET1 family histone methyltransferases. J Biol Chem. 2012;287:27275-89 pubmed publisher
    Translocations and amplifications of the mixed lineage leukemia-1 (MLL1) gene are associated with aggressive myeloid and lymphocytic leukemias in humans...
  9. Benedikt A, Baltruschat S, Scholz B, Bursen A, Arrey T, Meyer B, et al. The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures. Leukemia. 2011;25:135-44 pubmed publisher
    Expression of the AF4-MLL fusion protein in murine hematopoietic progenitor/stem cells results in the development of proB acute lymphoblastic leukemia...
  10. Xia Z, Anderson M, Diaz M, Zeleznik Le N. MLL repression domain interacts with histone deacetylases, the polycomb group proteins HPC2 and BMI-1, and the corepressor C-terminal-binding protein. Proc Natl Acad Sci U S A. 2003;100:8342-7 pubmed
    The MLL (mixed-lineage leukemia) gene is involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia...
  11. Balgobind B, Raimondi S, Harbott J, Zimmermann M, Alonzo T, Auvrignon A, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood. 2009;114:2489-96 pubmed publisher
    ..In most cases, the MLL gene is involved, and more than 50 translocation partners have been described...
  12. Dou Y, Milne T, Ruthenburg A, Lee S, Lee J, Verdine G, et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol. 2006;13:713-9 pubmed
    ..we report the first biochemical reconstitution of a functional four-component mixed-lineage leukemia protein-1 (MLL1) core complex...
  13. de Boer J, Walf Vorderwülbecke V, Williams O. In focus: MLL-rearranged leukemia. Leukemia. 2013;27:1224-8 pubmed publisher
    ..mechanisms underlying oncogenesis in leukemias associated with rearrangement of the Mixed Lineage Leukemia (MLL) gene have received a considerable amount of attention over the last two decades...
  14. Quentmeier H, Dirks W, MacLeod R, Reinhardt J, Zaborski M, Drexler H. Expression of HOX genes in acute leukemia cell lines with and without MLL translocations. Leuk Lymphoma. 2004;45:567-74 pubmed
    ..expression of the genes MEIS1, HOXA5, HOXA7 and HOXA9 has been reported to be correlated with the occurrence of MLL translocations...
  15. Sierra J, Yoshida T, Joazeiro C, Jones K. The APC tumor suppressor counteracts beta-catenin activation and H3K4 methylation at Wnt target genes. Genes Dev. 2006;20:586-600 pubmed
    ..The beta-cat C-terminal activation domain associates with TRRAP/TIP60 and mixed-lineage-leukemia (MLL1/MLL2) SET1-type chromatin-modifying complexes in vitro, and we show that beta-cat promotes H3K4 trimethylation at ..
  16. Tyagi S, Herr W. E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases. EMBO J. 2009;28:3185-95 pubmed publisher
    ..through a short DHQY sequence with the cell-cycle regulator HCF-1 together with the mixed-lineage leukaemia (MLL) family of histone H3 lysine 4 (H3K4) methyltransferases...
  17. Stumpel D, Schneider P, van Roon E, Boer J, de Lorenzo P, Valsecchi M, et al. Specific promoter methylation identifies different subgroups of MLL-rearranged infant acute lymphoblastic leukemia, influences clinical outcome, and provides therapeutic options. Blood. 2009;114:5490-8 pubmed publisher
    b>MLL-rearranged infant acute lymphoblastic leukemia (ALL) remains the most aggressive type of childhood leukemia, displaying a unique gene expression profile...
  18. Hsieh J, Ernst P, Erdjument Bromage H, Tempst P, Korsmeyer S. Proteolytic cleavage of MLL generates a complex of N- and C-terminal fragments that confers protein stability and subnuclear localization. Mol Cell Biol. 2003;23:186-94 pubmed
    The mixed-lineage leukemia gene (MLL, ALL1, HRX) encodes a 3,969-amino-acid nuclear protein homologous to Drosophila trithorax and is required to maintain proper Hox gene expression...
  19. Chang P, Hom R, Musselman C, Zhu L, Kuo A, Gozani O, et al. Binding of the MLL PHD3 finger to histone H3K4me3 is required for MLL-dependent gene transcription. J Mol Biol. 2010;400:137-44 pubmed publisher
    The MLL (mixed-lineage leukemia) proto-oncogene encodes a histone methyltransferase that creates the methylated histone H3K4 epigenetic marks, commonly associated with actively transcribed genes...
  20. 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. ..
  21. Bueno C, Ayllon V, Montes R, Navarro Montero O, Ramos Mejia V, Real P, et al. FLT3 activation cooperates with MLL-AF4 fusion protein to abrogate the hematopoietic specification of human ESCs. Blood. 2013;121:3867-78, S1-3 pubmed publisher
    Mixed-lineage leukemia (MLL)-AF4 fusion arises prenatally in high-risk infant acute pro-B-lymphoblastic leukemia (pro-B-ALL)...
  22. Song J, Kingston R. WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone H3-binding pocket. J Biol Chem. 2008;283:35258-64 pubmed publisher
    WDR5 is a component of the mixed lineage leukemia (MLL) complex, which methylates lysine 4 of histone H3, and was identified as a methylated Lys-4 histone H3-binding protein...
  23. Yokoyama A, Wang Z, Wysocka J, Sanyal M, Aufiero D, Kitabayashi I, et al. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol Cell Biol. 2004;24:5639-49 pubmed
    b>MLL (for mixed-lineage leukemia) is a proto-oncogene that is mutated in a variety of human leukemias...
  24. Tang Z, Chen W, Shimada M, Nguyen U, Kim J, Sun X, et al. SET1 and p300 act synergistically, through coupled histone modifications, in transcriptional activation by p53. Cell. 2013;154:297-310 pubmed publisher
    ..These results establish a mechanism in which SET1C and p300 act cooperatively, through direct interactions and coupled histone modifications, to facilitate the function of p53. ..
  25. Montes R, Ayllon V, Gutierrez Aranda I, Prat I, Hernández Lamas M, Ponce L, et al. Enforced expression of MLL-AF4 fusion in cord blood CD34+ cells enhances the hematopoietic repopulating cell function and clonogenic potential but is not sufficient to initiate leukemia. Blood. 2011;117:4746-58 pubmed publisher
    Infant acute lymphoblastic leukemia harboring the fusion mixed-lineage leukemia (MLL)-AF4 is associated with a dismal prognosis and very brief latency...
  26. Xia Z, Popovic R, Chen J, Theisler C, Stuart T, Santillan D, et al. The MLL fusion gene, MLL-AF4, regulates cyclin-dependent kinase inhibitor CDKN1B (p27kip1) expression. Proc Natl Acad Sci U S A. 2005;102:14028-33 pubmed
    b>MLL, involved in many chromosomal translocations associated with acute myeloid and lymphoid leukemia, has >50 known partner genes with which it is able to form in-frame fusions...
  27. Ziemin van der Poel S, McCabe N, Gill H, Espinosa R, Patel Y, Harden A, et al. Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias. Proc Natl Acad Sci U S A. 1991;88:10735-9 pubmed
    ..We have named this gene MLL (myeloid/lymphoid, or mixed-lineage, leukemia.
  28. Schlenk R, Dohner K, Kneba M, Götze K, Hartmann F, Del Valle F, et al. Gene mutations and response to treatment with all-trans retinoic acid in elderly patients with acute myeloid leukemia. Results from the AMLSG Trial AML HD98B. Haematologica. 2009;94:54-60 pubmed publisher
    ..Data from mutation analyses of the NPM1, CEBPA, FLT3, and MLL genes were correlated with outcome in patients 61 years and older treated within the AML HD98B trial...
  29. Stam R, den Boer M, Schneider P, de Boer J, Hagelstein J, Valsecchi M, et al. Association of high-level MCL-1 expression with in vitro and in vivo prednisone resistance in MLL-rearranged infant acute lymphoblastic leukemia. Blood. 2010;115:1018-25 pubmed publisher
    b>MLL-rearranged acute lymphoblastic leukemia (ALL) represents an unfavorable type of leukemia that often is highly resistant to glucocorticoids such as prednisone and dexamethasone...
  30. Wang Z, Smith K, Murphy M, Piloto O, Somervaille T, Cleary M. Glycogen synthase kinase 3 in MLL leukaemia maintenance and targeted therapy. Nature. 2008;455:1205-9 pubmed publisher
    ..in the maintenance of a specific subtype of poor prognosis human leukaemia, genetically defined by mutations of the MLL proto-oncogene...
  31. Chinwalla V, Chien A, Odero M, Neilly M, Zeleznik Le N, Rowley J. A t(11;15) fuses MLL to two different genes, AF15q14 and a novel gene MPFYVE on chromosome 15. Oncogene. 2003;22:1400-10 pubmed
    The mixed lineage leukemia gene (MLL, also known as HRX, ALL-1 and Htrx) located at 11q23 is involved in translocations with over 40 different chromosomal bands in a variety of leukemia subtypes...
  32. Liu H, Cheng E, Hsieh J. Bimodal degradation of MLL by SCFSkp2 and APCCdc20 assures cell cycle execution: a critical regulatory circuit lost in leukemogenic MLL fusions. Genes Dev. 2007;21:2385-98 pubmed
    Human chromosome 11q23 translocations disrupting MLL result in poor prognostic leukemias. It fuses the common MLL N-terminal approximately 1400 amino acids in-frame with >60 different partners without shared characteristics...
  33. Caslini C, Yang Z, El Osta M, Milne T, Slany R, Hess J. Interaction of MLL amino terminal sequences with menin is required for transformation. Cancer Res. 2007;67:7275-83 pubmed
    Rearrangements of the mixed lineage leukemia gene MLL are associated with aggressive lymphoid and myeloid leukemias...
  34. Ansari K, Hussain I, Das H, Mandal S. Overexpression of human histone methylase MLL1 upon exposure to a food contaminant mycotoxin, deoxynivalenol. FEBS J. 2009;276:3299-307 pubmed publisher
    ..inhibitors demonstrated that Src kinase families are involved in upstream events in DON-mediated upregulation of MLL1. Sequence analysis demonstrated that the MLL1 promoter contains multiple Sp1-binding sites and importantly, the ..
  35. Mohan M, Lin C, Guest E, Shilatifard A. Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis. Nat Rev Cancer. 2010;10:721-8 pubmed publisher
    ..RNA polymerase II (Pol II) elongation factor (ELL) was the first translocation partner of mixed lineage leukaemia (MLL) for which a biochemical function was determined...
  36. Muntean A, Tan J, Sitwala K, Huang Y, Bronstein J, Connelly J, et al. The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis. Cancer Cell. 2010;17:609-21 pubmed publisher
    b>MLL is involved in chromosomal rearrangements that generate fusion proteins with deregulated transcriptional activity. The mechanisms of MLL fusion protein-mediated transcriptional activation are poorly understood...
  37. Mishra B, Ansari K, Mandal S. Dynamic association of MLL1, H3K4 trimethylation with chromatin and Hox gene expression during the cell cycle. FEBS J. 2009;276:1629-40 pubmed publisher
    ..Interestingly, MLL1, which is normally associated with transcriptionally active chromatins (G1 phase), dissociates from condensed ..
  38. Meyer C, Burmeister T, Strehl S, Schneider B, Hubert D, Zach O, et al. Spliced MLL fusions: a novel mechanism to generate functional chimeric MLL-MLLT1 transcripts in t(11;19)(q23;p13.3) leukemia. Leukemia. 2007;21:588-90 pubmed
  39. Allen M, Grummitt C, Hilcenko C, Min S, Tonkin L, Johnson C, et al. Solution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia-associated MLL histone methyltransferase. EMBO J. 2006;25:4503-12 pubmed
    ..The mixed-lineage leukaemia (MLL) CXXC domain selectively binds nonmethyl-CpG DNA, and is required for transformation by MLL fusion proteins that ..
  40. 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...
  41. 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...
  42. Avdic V, Zhang P, Lanouette S, Voronova A, Skerjanc I, Couture J. Fine-tuning the stimulation of MLL1 methyltransferase activity by a histone H3-based peptide mimetic. FASEB J. 2011;25:960-7 pubmed publisher
    ..moiety to the N terminus of histone H3 significantly enhances its binding to WDR5 and prevents the stimulation of MLL1 methyltransferase activity by the WDR5-RbBP5-Ash2L complex...
  43. Huo H, Magro P, Pietsch E, Patel B, Scotto K. Histone methyltransferase MLL1 regulates MDR1 transcription and chemoresistance. Cancer Res. 2010;70:8726-35 pubmed publisher
    ..We show that the mixed lineage leukemia 1 (MLL1) protein, a histone methyltransferase specific for H3K4, is required for MDR1 promoter methylation, ..
  44. 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 ..
  45. Patel A, Vought V, Swatkoski S, Viggiano S, Howard B, Dharmarajan V, et al. Automethylation activities within the mixed lineage leukemia-1 (MLL1) core complex reveal evidence supporting a "two-active site" model for multiple histone H3 lysine 4 methylation. J Biol Chem. 2014;289:868-84 pubmed publisher
    The mixed lineage leukemia-1 (MLL1) core complex predominantly catalyzes mono- and dimethylation of histone H3 at lysine 4 (H3K4) and is frequently altered in aggressive acute leukemias...
  46. Southall S, Wong P, Odho Z, Roe S, Wilson J. Structural basis for the requirement of additional factors for MLL1 SET domain activity and recognition of epigenetic marks. Mol Cell. 2009;33:181-91 pubmed publisher
    The mixed-lineage leukemia protein MLL1 is a transcriptional regulator with an essential role in early development and hematopoiesis...
  47. Jansen M, Corral L, van der Velden V, Panzer Grümayer R, Schrappe M, Schrauder A, et al. Immunobiological diversity in infant acute lymphoblastic leukemia is related to the occurrence and type of MLL gene rearrangement. Leukemia. 2007;21:633-41 pubmed
    ..Ig) and T-cell receptor (TCR) gene rearrangement pattern, and the presence of mixed lineage leukemia (MLL) rearrangements...
  48. Risner L, Kuntimaddi A, Lokken A, Achille N, Birch N, Schoenfelt K, et al. Functional specificity of CpG DNA-binding CXXC domains in mixed lineage leukemia. J Biol Chem. 2013;288:29901-10 pubmed publisher
    The MLL CXXC domain binds nonmethylated CpG-containing DNA and is essential for the oncogenic properties of MLL fusion proteins...
  49. Zhang P, Lee H, Brunzelle J, Couture J. The plasticity of WDR5 peptide-binding cleft enables the binding of the SET1 family of histone methyltransferases. Nucleic Acids Res. 2012;40:4237-46 pubmed publisher
    In mammals, the SET1 family of lysine methyltransferases (KMTs), which includes MLL1-5, SET1A and SET1B, catalyzes the methylation of lysine-4 (Lys-4) on histone H3...
  50. Patel A, Dharmarajan V, Vought V, Cosgrove M. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. J Biol Chem. 2009;284:24242-56 pubmed publisher
    ..The mixed lineage leukemia protein-1 (MLL1) is a member of the SET1 family of H3K4 methyltransferases and is frequently rearranged in acute leukemias...
  51. Djabali M, Selleri L, Parry P, Bower M, Young B, Evans G. A trithorax-like gene is interrupted by chromosome 11q23 translocations in acute leukaemias. Nat Genet. 1992;2:113-8 pubmed
    ..An analysis of a series of leukaemic patients carrying t(4;11) and t(9;11) translocations indicate that the majority of breakpoints in infant leukaemias lie within a 5 kb region. ..
  52. Patel A, Vought V, Dharmarajan V, Cosgrove M. A conserved arginine-containing motif crucial for the assembly and enzymatic activity of the mixed lineage leukemia protein-1 core complex. J Biol Chem. 2008;283:32162-75 pubmed publisher
    The mixed lineage leukemia protein-1 (MLL1) belongs to the SET1 family of histone H3 lysine 4 methyltransferases...
  53. 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...
  54. Wysocka J, Swigut T, Milne T, Dou Y, Zhang X, Burlingame A, et al. WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4 methylation and vertebrate development. Cell. 2005;121:859-72 pubmed
    ..Here we show that a common component of MLL1, MLL2, and hSet1 H3 K4 methyltransferase complexes, the WD40-repeat protein WDR5, directly associates with histone ..
  55. 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...
  56. Tyagi S, Chabes A, Wysocka J, Herr W. E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Mol Cell. 2007;27:107-19 pubmed
    ..During the G1-to-S phase transition, HCF-1 recruits the mixed-lineage leukemia (MLL) and Set-1 histone H3 lysine 4 methyltransferases to E2F-responsive promoters and induces histone methylation and ..
  57. Patel A, Dharmarajan V, Cosgrove M. Structure of WDR5 bound to mixed lineage leukemia protein-1 peptide. J Biol Chem. 2008;283:32158-61 pubmed publisher
    The mixed lineage leukemia protein-1 (MLL1) catalyzes histone H3 lysine 4 methylation and is regulated by interaction with WDR5 (WD-repeat protein-5), RbBP5 (retinoblastoma-binding protein-5), and the Ash2L (absent, small, homeotic discs-..
  58. Cierpicki T, Risner L, Grembecka J, Lukasik S, Popovic R, Omonkowska M, et al. Structure of the MLL CXXC domain-DNA complex and its functional role in MLL-AF9 leukemia. Nat Struct Mol Biol. 2010;17:62-8 pubmed publisher
    The gene MLL (encoding the protein mixed-lineage leukemia) is the target of chromosomal translocations that cause leukemias with poor prognosis...
  59. Krivtsov A, Armstrong S. MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer. 2007;7:823-33 pubmed
    Translocations that involve the mixed lineage leukaemia (MLL) gene identify a unique group of acute leukaemias, and often predict a poor prognosis...
  60. Yokoyama A, Somervaille T, Smith K, Rozenblatt Rosen O, Meyerson M, Cleary M. The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis. Cell. 2005;123:207-18 pubmed
    The Mixed-Lineage Leukemia (MLL) protein is a histone methyltransferase that is mutated in clinically and biologically distinctive subsets of acute leukemia...
  61. Wu L, Zee B, Wang Y, Garcia B, Dou Y. The RING finger protein MSL2 in the MOF complex is an E3 ubiquitin ligase for H2B K34 and is involved in crosstalk with H3 K4 and K79 methylation. Mol Cell. 2011;43:132-44 pubmed publisher
    ..e., H4 K16 acetylation and H2B K34 ubiquitylation) through MOF and MSL2 subunits. They also shed light on how an intricate network of chromatin-modifying enzymes functions coordinately in gene activation. ..
  62. Whitman S, Liu S, Vukosavljevic T, Rush L, Yu L, Liu C, et al. The MLL partial tandem duplication: evidence for recessive gain-of-function in acute myeloid leukemia identifies a novel patient subgroup for molecular-targeted therapy. Blood. 2005;106:345-52 pubmed
    b>MLL (ALL-1) chimeric fusions and MLL partial tandem duplications (PTD) may have mechanistically distinct contributions to leukemogenesis...
  63. Cao F, Chen Y, Cierpicki T, Liu Y, Basrur V, Lei M, et al. An Ash2L/RbBP5 heterodimer stimulates the MLL1 methyltransferase activity through coordinated substrate interactions with the MLL1 SET domain. PLoS ONE. 2010;5:e14102 pubmed publisher
    ..We demonstrate that both Ash2L and the MLL1 SET domain are capable of binding to S-adenosyl-L- [methyl-(3)H] methionine in the MLL1 core complex...
  64. Ferrando A, Armstrong S, Neuberg D, Sallan S, Silverman L, Korsmeyer S, et al. Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation. Blood. 2003;102:262-8 pubmed
    Rearrangements of the MLL locus, located on human chromosome 11q23, are frequent in both infant and therapy-related leukemias...
  65. 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...
  66. Nakamura T, Mori T, Tada S, Krajewski W, Rozovskaia T, Wassell R, et al. ALL-1 is a histone methyltransferase that assembles a supercomplex of proteins involved in transcriptional regulation. Mol Cell. 2002;10:1119-28 pubmed
    ..In parallel, H3-K4 is methylated, and histones H3 and H4 are acetylated at this promoter. ..
  67. Fair K, Anderson M, Bulanova E, Mi H, Tropschug M, Diaz M. Protein interactions of the MLL PHD fingers modulate MLL target gene regulation in human cells. Mol Cell Biol. 2001;21:3589-97 pubmed
    The PHD fingers of the human MLL and Drosophila trx proteins have strong amino acid sequence conservation but their function is unknown...
  68. Blobel G, Kadauke S, Wang E, Lau A, Zuber J, Chou M, et al. A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit. Mol Cell. 2009;36:970-83 pubmed publisher
    Mixed lineage leukemia (MLL) and its metazoan Trithorax orthologs have been linked with the epigenetic maintenance of transcriptional activity...
  69. Caslini C, Connelly J, Serna A, Broccoli D, Hess J. MLL associates with telomeres and regulates telomeric repeat-containing RNA transcription. Mol Cell Biol. 2009;29:4519-26 pubmed publisher
    ..Here, we show that the histone 3/lysine 4 (H3/K4) HMT and the transcriptional regulator MLL associate with telomeres and contribute to their H3/K4 methylation and transcription in a telomere length-dependent ..
  70. Schafer E, Irizarry R, Negi S, McIntyre E, Small D, Figueroa M, et al. Promoter hypermethylation in MLL-r infant acute lymphoblastic leukemia: biology and therapeutic targeting. Blood. 2010;115:4798-809 pubmed publisher
    Cooperating leukemogenic events in MLL-rearranged (MLL-r) infant acute lymphoblastic leukemia (ALL) are largely unknown...
  71. Ansari K, Mishra B, Mandal S. Human CpG binding protein interacts with MLL1, MLL2 and hSet1 and regulates Hox gene expression. Biochim Biophys Acta. 2008;1779:66-73 pubmed
    Human encodes several histone H3-Lysine 4 (H3K4) specific methyl-transferases (HMTs) such as MLL1 (mixed lineage leukemia 1), MLL2, MLL3, hSet1 etc, that play critical roles in gene expression...
  72. Thirman M, Gill H, Burnett R, Mbangkollo D, McCabe N, Kobayashi H, et al. Rearrangement of the MLL gene in acute lymphoblastic and acute myeloid leukemias with 11q23 chromosomal translocations. N Engl J Med. 1993;329:909-14 pubmed
    ..breakpoint region in leukemias with the common 11q23 translocations and subsequently cloned a gene named MLL that spans the 11q23 breakpoint. We isolated a 0...