Kmt2d

Summary

Gene Symbol: Kmt2d
Description: lysine (K)-specific methyltransferase 2D
Alias: ALR, BC032281, BC058659, C430014K11Rik, KMT2B, Mll2, Mll4, histone-lysine N-methyltransferase 2D, ALL1-related protein, histone-lysine N-methyltransferase MLL2, lysine N-methyltransferase 2B, lysine N-methyltransferase 2D, myeloid/lymphoid or mixed-lineage leukemia 2, myeloid/lymphoid or mixed-lineage leukemia protein 2
Species: mouse
Products:     Kmt2d

Top Publications

  1. Glaser S, Schaft J, Lubitz S, Vintersten K, van der Hoeven F, Tufteland K, et al. Multiple epigenetic maintenance factors implicated by the loss of Mll2 in mouse development. Development. 2006;133:1423-32 pubmed
    ..To look for evidence of gene-specific epigenetic regulation in mammalian development, we examined one of these six, Mll2, using a multipurpose allele in the mouse to ascertain the loss-of-function phenotype...
  2. Lubitz S, Glaser S, Schaft J, Stewart A, Anastassiadis K. Increased apoptosis and skewed differentiation in mouse embryonic stem cells lacking the histone methyltransferase Mll2. Mol Biol Cell. 2007;18:2356-66 pubmed
    ..The histone 3 lysine 4 methyltransferase Mll2/Wbp7 is essential for embryonic development...
  3. 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
    ..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)...
  4. 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
    ..In this study, we identify MLL4 (KMT2D) as a major mammalian H3K4 mono- and di-methyltransferase with partial functional redundancy with MLL3 (KMT2C)...
  5. 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...
  6. Kim D, Kim J, Kwon J, Sandhu J, Tontonoz P, Lee S, et al. Critical Roles of the Histone Methyltransferase MLL4/KMT2D in Murine Hepatic Steatosis Directed by ABL1 and PPAR?2. Cell Rep. 2016;17:1671-1682 pubmed publisher
    ..Here, we report that the histone H3 lysine 4 methyltransferase MLL4/KMT2D directs overnutrition-induced murine steatosis via its coactivator function for PPAR?2...
  7. Hughes C, Rozenblatt Rosen O, Milne T, Copeland T, Levine S, Lee J, et al. Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus. Mol Cell. 2004;13:587-97 pubmed
    ..show that menin is associated with a histone methyltransferase complex containing two trithorax family proteins, MLL2 and Ash2L, and other homologs of the yeast Set1 assembly...
  8. 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. ..
  9. Ortega Molina A, Boss I, Canela A, Pan H, Jiang Y, Zhao C, et al. The histone lysine methyltransferase KMT2D sustains a gene expression program that represses B cell lymphoma development. Nat Med. 2015;21:1199-208 pubmed publisher
    The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D ..

More Information

Publications40

  1. Scoville D, Cyphert H, Liao L, Xu J, Reynolds A, Guo S, et al. MLL3 and MLL4 Methyltransferases Bind to the MAFA and MAFB Transcription Factors to Regulate Islet β-Cell Function. Diabetes. 2015;64:3772-83 pubmed publisher
    ..Among the many coregulators identified were all of the subunits of the mixed-lineage leukemia 3 (Mll3) and 4 (Mll4) complexes, with histone 3 lysine 4 methyltransferases strongly associated with gene activation...
  2. 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...
  3. Denissov S, Hofemeister H, Marks H, Kranz A, Ciotta G, Singh S, et al. Mll2 is required for H3K4 trimethylation on bivalent promoters in embryonic stem cells, whereas Mll1 is redundant. Development. 2014;141:526-37 pubmed publisher
    ..Here, we show that Mll2, one of the six Set1/Trithorax-type H3K4 methyltransferases in mammals, is required for trimethylation of bivalent ..
  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. Hu D, Gao X, Cao K, Morgan M, Mas G, Smith E, et al. Not All H3K4 Methylations Are Created Equal: Mll2/COMPASS Dependency in Primordial Germ Cell Specification. Mol Cell. 2017;65:460-475.e6 pubmed publisher
    ..Here, we show that in addition to implementing H3K4me3 at promoters of bivalent genes, Mll2 (KMT2B)/COMPASS can also implement H3K4me3 at a subset of non-TSS regulatory elements, a subset of which shares ..
  6. 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...
  7. Andreu Vieyra C, Chen R, Agno J, Glaser S, Anastassiadis K, Stewart A, et al. MLL2 is required in oocytes for bulk histone 3 lysine 4 trimethylation and transcriptional silencing. PLoS Biol. 2010;8: pubmed publisher
    ..Here we show that the histone 3 lysine 4 (H3K4) methyltransferase, MLL2, controls most of the promoter-specific chromatin modification, H3K4me3, during oogenesis and early development...
  8. 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
    ..family, which includes Trr in Drosophila melanogaster and MLL3 (encoded by KMT2C) and MLL4 (encoded by KMT2D) in mammals...
  9. Mo R, Rao S, Zhu Y. Identification of the MLL2 complex as a coactivator for estrogen receptor alpha. J Biol Chem. 2006;281:15714-20 pubmed
    A novel estrogen receptor (ER)alpha coactivator complex, the MLL2 complex, which consists of MLL2, ASH2, RBQ3, and WDR5, was identified...
  10. Dai Q, Shen Y, Wang Y, Wang X, Francisco J, Luo Z, et al. Striking a balance: regulation of transposable elements by Zfp281 and Mll2 in mouse embryonic stem cells. Nucleic Acids Res. 2017;45:12301-12310 pubmed publisher
    ..The COMPASS-like H3K4 methyltransferase Mll2 is the major H3K4me3 methylase at the Zfp281-regulated L1s and required for their proper expression...
  11. Goldsworthy M, Absalom N, Schröter D, Matthews H, Bogani D, Moir L, et al. Mutations in Mll2, an H3K4 methyltransferase, result in insulin resistance and impaired glucose tolerance in mice. PLoS ONE. 2013;8:e61870 pubmed publisher
    ..Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7) gene causes type 2 diabetes in the mouse...
  12. 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
    ..editing to separate catalytic activity-dependent and independent functions of Mll3 (Kmt2c) and Mll4 (Kmt2d, Mll2), the major enhancer H3K4 monomethyltransferases...
  13. Tan C, Sindhu K, Li S, Nishio H, Stoller J, Oishi K, et al. Transcription factor Ap2delta associates with Ash2l and ALR, a trithorax family histone methyltransferase, to activate Hoxc8 transcription. Proc Natl Acad Sci U S A. 2008;105:7472-7 pubmed publisher
    ..associates with endogenous ASH2L and a member of the MLL family of histone lysine methyltransferases (HKMTs), MLL2 (ALR), forming a complex that methylates lysine 4 of histone H3 (H3K4)...
  14. Santos M, Faryabi R, Ergen A, Day A, Malhowski A, Canela A, et al. DNA-damage-induced differentiation of leukaemic cells as an anti-cancer barrier. Nature. 2014;514:107-11 pubmed publisher
    ..Here we show that the histone methyl-transferase MLL4, a suppressor of B-cell lymphoma, is required for stem-cell activity and an aggressive form of acute myeloid ..
  15. Wang S, Tang Z, Chen C, Shimada M, Koche R, Wang L, et al. A UTX-MLL4-p300 Transcriptional Regulatory Network Coordinately Shapes Active Enhancer Landscapes for Eliciting Transcription. Mol Cell. 2017;67:308-321.e6 pubmed publisher
    ..Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300...
  16. Placek K, Hu G, Cui K, Zhang D, Ding Y, Lee J, et al. MLL4 prepares the enhancer landscape for Foxp3 induction via chromatin looping. Nat Immunol. 2017;18:1035-1045 pubmed publisher
    b>MLL4 is an essential subunit of the histone H3 Lys4 (H3K4)-methylation complexes...
  17. Zhang J, Dominguez Sola D, Hussein S, Lee J, Holmes A, Bansal M, et al. Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis. Nat Med. 2015;21:1190-8 pubmed publisher
    Mutations in the gene encoding the KMT2D (or MLL2) methyltransferase are highly recurrent and occur early during tumorigenesis in diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL)...
  18. Benjamin J, Pilarowski G, Carosso G, Zhang L, Huso D, Goff L, et al. A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome. Proc Natl Acad Sci U S A. 2017;114:125-130 pubmed publisher
    Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility...
  19. Jang Y, Wang C, Zhuang L, Liu C, Ge K. H3K4 Methyltransferase Activity Is Required for MLL4 Protein Stability. J Mol Biol. 2017;429:2046-2054 pubmed publisher
    ..Enhancers are marked by histone H3K4 mono- and di-methylation (H3K4me1/2). The tumor suppressor MLL4 (KMT2D) is a major enhancer H3K4 mono- and di-methyltransferase with a partial functional redundancy with MLL3 (KMT2C)...
  20. Bjornsson H, Benjamin J, Zhang L, Weissman J, Gerber E, Chen Y, et al. Histone deacetylase inhibition rescues structural and functional brain deficits in a mouse model of Kabuki syndrome. Sci Transl Med. 2014;6:256ra135 pubmed publisher
    ..of Kabuki syndrome with a heterozygous deletion in the gene encoding the lysine-specific methyltransferase 2D (Kmt2d), leading to impairment of methyltransferase function...
  21. Wang C, Lee J, Lai B, Macfarlan T, Xu S, Zhuang L, et al. Enhancer priming by H3K4 methyltransferase MLL4 controls cell fate transition. Proc Natl Acad Sci U S A. 2016;113:11871-11876 pubmed
    ..Active enhancers are further marked by H3K27 acetylation (H3K27ac). Mixed-lineage leukemia 4 (MLL4/KMT2D) is a major enhancer H3K4me1/2 methyltransferase with functional redundancy with MLL3 (KMT2C)...
  22. Ang S, Uebersohn A, Spencer C, Huang Y, Lee J, Ge K, et al. KMT2D regulates specific programs in heart development via histone H3 lysine 4 di-methylation. Development. 2016;143:810-21 pubmed publisher
    b>KMT2D, which encodes a histone H3K4 methyltransferase, has been implicated in human congenital heart disease in the context of Kabuki syndrome. However, its role in heart development is not understood...
  23. Kantidakis T, Saponaro M, Mitter R, Horswell S, Kranz A, Boeing S, et al. Mutation of cancer driver MLL2 results in transcription stress and genome instability. Genes Dev. 2016;30:408-20 pubmed publisher
    Genome instability is a recurring feature of tumorigenesis. Mutation in MLL2, encoding a histone methyltransferase, is a driver in numerous different cancer types, but the mechanism is unclear...
  24. Ladopoulos V, Hofemeister H, Hoogenkamp M, Riggs A, Stewart A, Bonifer C. The histone methyltransferase KMT2B is required for RNA polymerase II association and protection from DNA methylation at the MagohB CpG island promoter. Mol Cell Biol. 2013;33:1383-93 pubmed publisher
    b>KMT2B (MLL2/WBP7) is a member of the MLL subfamily of H3K4-specific histone lysine methyltransferases (KMT2) and is vital for normal embryonic development in the mouse...
  25. 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
    ..Thus, arginine methylation of Pax7 by Carm1 functions as a molecular switch controlling the epigenetic induction of Myf5 during satellite stem cell asymmetric division and entry into the myogenic program. ..
  26. Demers C, Chaturvedi C, Ranish J, Juban G, Lai P, Morle F, et al. Activator-mediated recruitment of the MLL2 methyltransferase complex to the beta-globin locus. Mol Cell. 2007;27:573-84 pubmed
    ..However, it is unclear how MLL complexes are targeted to specific gene loci. Here, we show that the MLL2 complex associates with the hematopoietic activator NF-E2 in erythroid cells and is important for H3K4 ..
  27. 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 deficiency results in noncleavage (nc) of MLL and MLL2 and homeotic transformations...
  28. 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...
  29. Hu D, Gao X, Morgan M, Herz H, Smith E, Shilatifard A. The MLL3/MLL4 branches of the COMPASS family function as major histone H3K4 monomethylases at enhancers. Mol Cell Biol. 2013;33:4745-54 pubmed publisher
    ..There are six COMPASS family members in mammals, two of which, MLL3 (GeneID 58508) and MLL4 (GeneID 8085), are most closely related to Drosophila Trr...
  30. 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
    ..that include retinoic acid receptor (RAR), associates with histone H3-K4 methyltranferases (H3K4MTs) MLL3 and MLL4 in mixed-lineage leukemia...
  31. Piazza F, Costoya J, Merghoub T, Hobbs R, Pandolfi P. Disruption of PLZP in mice leads to increased T-lymphocyte proliferation, cytokine production, and altered hematopoietic stem cell homeostasis. Mol Cell Biol. 2004;24:10456-69 pubmed
    ..PLZP gene through in-frame insertion of a lacZ reporter and without perturbing the expression of the neighboring MLL2 gene...