Kmt2c

Summary

Gene Symbol: Kmt2c
Description: lysine (K)-specific methyltransferase 2C
Alias: E330008K23Rik, HALR, Mll3, mKIAA1506, histone-lysine N-methyltransferase 2C, histone-lysine N-methyltransferase MLL3, lysine N-methyltransferase 2C, myeloid/lymphoid or mixed-lineage leukemia 3, myeloid/lymphoid or mixed-lineage leukemia protein 3 homolog
Species: mouse
Products:     Kmt2c

Top Publications

  1. 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...
  2. Lee J, Saha P, Yang Q, Lee S, Park J, Suh Y, et al. Targeted inactivation of MLL3 histone H3-Lys-4 methyltransferase activity in the mouse reveals vital roles for MLL3 in adipogenesis. Proc Natl Acad Sci U S A. 2008;105:19229-34 pubmed publisher
    ..receptor gamma (PPARgamma) and C/EBPalpha, is associated with histone H3-Lys-4-methyltransferase (H3K4MT) MLL3 or its paralogue MLL4 in a complex named ASCOM (ASC-2 complex)...
  3. Brun M, Gasca S, Girard C, Bouton K, de Massy B, De Sario A. Characterization and expression analysis during embryo development of the mouse ortholog of MLL3. Gene. 2006;371:25-33 pubmed
    We characterized the mouse ortholog of the human MLL3 gene and a 10.6 kb-Mll3 transcript. The mouse Mll3 gene comprises 60 exons that encompass 226 kb in chromosome 5...
  4. Dorighi K, Swigut T, Henriques T, Bhanu N, Scruggs B, Nady N, et al. Mll3 and Mll4 Facilitate Enhancer RNA Synthesis and Transcription from Promoters Independently of H3K4 Monomethylation. Mol Cell. 2017;66:568-576.e4 pubmed publisher
    ..we used CRISPR/Cas9 genome editing to separate catalytic activity-dependent and independent functions of Mll3 (Kmt2c) and Mll4 (Kmt2d, Mll2), the major enhancer H3K4 monomethyltransferases...
  5. Lai B, Lee J, Jang Y, Wang L, Peng W, Ge K. MLL3/MLL4 are required for CBP/p300 binding on enhancers and super-enhancer formation in brown adipogenesis. Nucleic Acids Res. 2017;45:6388-6403 pubmed publisher
    Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers...
  6. Dahl J, Jung I, Aanes H, Greggains G, Manaf A, Lerdrup M, et al. Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition. Nature. 2016;537:548-552 pubmed publisher
    ..Our results provide insight into the onset of the developmental program in mouse embryos and demonstrate a role for broad H3K4me3 domains in MZT. ..
  7. Chen C, Liu Y, Rappaport A, Kitzing T, Schultz N, Zhao Z, et al. MLL3 is a haploinsufficient 7q tumor suppressor in acute myeloid leukemia. Cancer Cell. 2014;25:652-65 pubmed publisher
    ..RNAi and CRISPR/Cas9 approaches, we show that an ?50% reduction in gene dosage of the mixed lineage leukemia 3 (MLL3) gene, located on 7q36.1, cooperates with other events occurring in -7/del(7q) AMLs to promote leukemogenesis...
  8. Lee J, Wang C, Xu S, Cho Y, Wang L, Feng X, et al. H3K4 mono- and di-methyltransferase MLL4 is required for enhancer activation during cell differentiation. elife. 2013;2:e01503 pubmed publisher
    ..KMT2D) as a major mammalian H3K4 mono- and di-methyltransferase with partial functional redundancy with MLL3 (KMT2C)...
  9. Kim D, Lee J, Lee B, Lee J. ASCOM controls farnesoid X receptor transactivation through its associated histone H3 lysine 4 methyltransferase activity. Mol Endocrinol. 2009;23:1556-62 pubmed publisher
    ..a steady-state complex named ASCOM (for ASC-2 complex), which contains histone H3 lysine 4 (H3K4) methyltransferase MLL3 or its paralog MLL4...

More Information

Publications24

  1. Mann K, Ward J, Yew C, Kovochich A, Dawson D, Black M, et al. Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma. Proc Natl Acad Sci U S A. 2012;109:5934-41 pubmed publisher
    ..these tumors, we identified 681 loci that comprise 543 candidate cancer genes (CCGs); 75 of these CCGs, including Mll3 and Ptk2, have known mutations in human pancreatic cancer...
  2. Valekunja U, Edgar R, Oklejewicz M, van der Horst G, O Neill J, Tamanini F, et al. Histone methyltransferase MLL3 contributes to genome-scale circadian transcription. Proc Natl Acad Sci U S A. 2013;110:1554-9 pubmed publisher
    ..Importantly, catalytic inactivation of the histone methyltransferase activity of MLL3 also severely compromises the oscillation of "core" clock gene promoters, including Bmal1, mCry1, mPer2, and Rev-..
  3. Shao G, Chen J, Zhang L, Huang P, Lu H, Jin J, et al. Dynamic patterns of histone H3 lysine 4 methyltransferases and demethylases during mouse preimplantation development. In Vitro Cell Dev Biol Anim. 2014;50:603-13 pubmed publisher
    ..Herein, the authors examined the dynamic changes of H3K4me and its key regulators (Ash1l, Ash2l, Kmt2a, Kmt2b, Kmt2c, Setd1a, Setd7, Kdm1a, Kdm1b, Kdm5a, Kdm5b, Kdm5c, and Kdm5d) in mouse oocytes and preimplantation embryos...
  4. Starnes L, Su D, Pikkupeura L, Weinert B, Santos M, Mund A, et al. A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex. Genes Dev. 2016;30:149-63 pubmed publisher
    ..Although PTIP is a unique component of the mixed-lineage leukemia 3 (MLL3)/MLL4 chromatin-modifying complex, the mechanisms for how PTIP promotes transcription remain unclear...
  5. Arcipowski K, Bulic M, Gurbuxani S, Licht J. Loss of Mll3 Catalytic Function Promotes Aberrant Myelopoiesis. PLoS ONE. 2016;11:e0162515 pubmed publisher
    ..minimally deleted region in 7q, includes the gene encoding the histone methyltransferase mixed-lineage leukemia 3 (MLL3), which is also mutated in a small percentage of AML patients...
  6. 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
    ..However, the loss of MLL3/MLL4 and/or the Set1 complexes has little to no effect on the H3K4 methylation of Hox loci or their expression ..
  7. Lee S, Lee D, Dou Y, Lee J, Lee B, Kwak E, et al. Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases. Proc Natl Acad Sci U S A. 2006;103:15392-7 pubmed
    ..factors that include retinoic acid receptor (RAR), associates with histone H3-K4 methyltranferases (H3K4MTs) MLL3 and MLL4 in mixed-lineage leukemia...
  8. Kim D, Rhee J, Yeo S, Shen R, Lee S, Lee J, et al. Crucial roles of mixed-lineage leukemia 3 and 4 as epigenetic switches of the hepatic circadian clock controlling bile acid homeostasis in mice. Hepatology. 2015;61:1012-23 pubmed publisher
    The histone H3-lysine-4 methyltransferase mixed-lineage leukemia 3 (MLL3) and its closest homolog, MLL4 (aka KMT2D), belong to two homologous transcriptional coactivator complexes, named MLL3 and MLL4 complexes, respectively...
  9. Nakagawa T, Kajitani T, Togo S, Masuko N, Ohdan H, Hishikawa Y, et al. Deubiquitylation of histone H2A activates transcriptional initiation via trans-histone cross-talk with H3K4 di- and trimethylation. Genes Dev. 2008;22:37-49 pubmed publisher
    ..Our studies revealed a novel mode of trans-histone cross-talk, in which H2A ubiquitylation controls the di- and trimethylation of H3K4, resulting in regulation of transcriptional initiation. ..
  10. Zhang Z, Christin J, Wang C, Ge K, Oktay M, Guo W. Mammary-Stem-Cell-Based Somatic Mouse Models Reveal Breast Cancer Drivers Causing Cell Fate Dysregulation. Cell Rep. 2016;16:3146-3156 pubmed publisher
    ..RNAi and CRISPR-mediated genome engineering in MaSC-GEMMs, we have discovered that inactivation of Ptpn22 or Mll3, two genes mutated in human breast cancer, greatly accelerated PI3K-driven mammary tumorigenesis...
  11. Ananthanarayanan M, Li Y, Surapureddi S, Balasubramaniyan N, Ahn J, Goldstein J, et al. Histone H3K4 trimethylation by MLL3 as part of ASCOM complex is critical for NR activation of bile acid transporter genes and is downregulated in cholestasis. Am J Physiol Gastrointest Liver Physiol. 2011;300:G771-81 pubmed publisher
    ..Using a microarray, we identified decreased expression of mixed lineage leukemia 3 (MLL3), a histone H3 lysine 4 (H3K4) lysine methyl transferase at 1 and 3 days of post-common bile duct ligation (CBDL) ..
  12. Lee J, Kim D, Lee S, Yang Q, Lee D, Lee S, et al. A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4. Proc Natl Acad Sci U S A. 2009;106:8513-8 pubmed publisher
    ..complex, named ASCOM (for ASC-2 COMplex), that contains the histone H3-lysine-4 (H3K4)-methyltransferase MLL3 or its paralogue MLL4...
  13. Lee S, Lee J, Lee S, Lee J. Activating signal cointegrator-2 is an essential adaptor to recruit histone H3 lysine 4 methyltransferases MLL3 and MLL4 to the liver X receptors. Mol Endocrinol. 2008;22:1312-9 pubmed publisher
    ..including the liver X receptors (LXRs), is associated with histone H3 lysine 4 (H3K4) methyltransferase (H3K4MT) MLL3 or its paralogue MLL4 in a steady-state complex named ASCOM (ASC-2 complex)...
  14. Tan Y, Chow V. 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. Cancer Detect Prev. 2001;25:454-69 pubmed
    ..12-kb cDNA of a novel human gene (designated HALR for "homologous to ALR" and given the symbol MLL3 by the HUGO Gene Nomenclature Committee) for which open reading frame (ORF) encodes a predicted large hydrophilic ..
  15. Rickels R, Herz H, Sze C, Cao K, Morgan M, Collings C, et al. Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability. Nat Genet. 2017;49:1647-1653 pubmed publisher
    ..by the COMPASS-like methyltransferase family, which includes Trr in Drosophila melanogaster and MLL3 (encoded by KMT2C) and MLL4 (encoded by KMT2D) in mammals...