Gene Symbol: ESET
Description: SET domain, bifurcated 1
Alias: AU022152, ESET, KMT1E, mKIAA0067, histone-lysine N-methyltransferase SETDB1, ERG-associated protein with SET domain, SET domain ERG-associated histone methyltransferase
Species: mouse
Products:     ESET

Top Publications

  1. Lawson K, Teteak C, Gao J, Li N, Hacquebord J, Ghatan A, et al. ESET histone methyltransferase regulates osteoblastic differentiation of mesenchymal stem cells during postnatal bone development. FEBS Lett. 2013;587:3961-7 pubmed publisher
    To investigate the effects of histone methyltransferase ESET (also known as SETDB1) on bone metabolism, we analyzed osteoblasts and osteoclasts in ESET knockout animals, and performed osteogenesis assays using ESET-null mesenchymal stem ..
  2. Lohmann F, Loureiro J, Su H, Fang Q, Lei H, Lewis T, et al. KMT1E mediated H3K9 methylation is required for the maintenance of embryonic stem cells by repressing trophectoderm differentiation. Stem Cells. 2010;28:201-12 pubmed publisher
    ..The histone H3K9 methyltransferase KMT1E, formerly known as ESET or Setdb1, is essential to embryonic development as the ablation of the Setdb1 gene ..
  3. Karimi M, Goyal P, Maksakova I, Bilenky M, Leung D, Tang J, et al. DNA methylation and SETDB1/H3K9me3 regulate predominantly distinct sets of genes, retroelements, and chimeric transcripts in mESCs. Cell Stem Cell. 2011;8:676-87 pubmed publisher
    ..Thus, SETDB1 plays a previously unappreciated yet critical role in inhibiting aberrant gene transcription by suppressing the expression of proximal ERVs...
  4. Dodge J, Kang Y, Beppu H, Lei H, Li E. Histone H3-K9 methyltransferase ESET is essential for early development. Mol Cell Biol. 2004;24:2478-86 pubmed
    ..b>ESET, G9a, SUV39-h1, SUV39-h2, and Eu-HMTase are histone methyltransferases that catalyze H3-K9 methylation in mammalian ..
  5. Leung D, Du T, Wagner U, Xie W, Lee A, Goyal P, et al. Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1. Proc Natl Acad Sci U S A. 2014;111:6690-5 pubmed publisher
  6. Matsui T, Leung D, Miyashita H, Maksakova I, Miyachi H, Kimura H, et al. Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature. 2010;464:927-31 pubmed publisher
    ..Here we show that the H3K9 methyltransferase ESET (also called SETDB1 or KMT1E) and the Kr├╝ppel-associated box (KRAB)-associated protein 1 (KAP1, also called TRIM28) are required for H3K9me3 ..
  7. Yuan P, Han J, Guo G, Orlov Y, Huss M, Loh Y, et al. Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells. Genes Dev. 2009;23:2507-20 pubmed publisher
    The histone H3 Lys 9 (H3K9) methyltransferase Eset is an epigenetic regulator critical for the development of the inner cell mass (ICM)...
  8. Liu S, Brind Amour J, Karimi M, Shirane K, Bogutz A, Lefebvre L, et al. Setdb1 is required for germline development and silencing of H3K9me3-marked endogenous retroviruses in primordial germ cells. Genes Dev. 2014;28:2041-55 pubmed publisher
    ..5 PGCs and postnatal hypogonadism in both sexes. Taken together, these observations reveal that SETDB1 is an essential guardian against proviral expression prior to the onset of de novo DNA methylation in the germline. ..
  9. Bilodeau S, Kagey M, Frampton G, Rahl P, Young R. SetDB1 contributes to repression of genes encoding developmental regulators and maintenance of ES cell state. Genes Dev. 2009;23:2484-9 pubmed publisher
    ..These genes are subjected to repression by both Polycomb group proteins and SetDB1, and loss of either regulator can destabilize ES cell state. ..

More Information


  1. Yang L, Xia L, Wu D, Wang H, Chansky H, Schubach W, et al. Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor. Oncogene. 2002;21:148-52 pubmed
    ..6 kb full-length mouse cDNA encoding a 1307-amino acid protein migrating as a 180 kD band, which was termed ESET (ERG-associated protein with SET domain)...
  2. Collins P, Kyle K, Egawa T, Shinkai Y, Oltz E. The histone methyltransferase SETDB1 represses endogenous and exogenous retroviruses in B lymphocytes. Proc Natl Acad Sci U S A. 2015;112:8367-72 pubmed publisher
    ..These findings have important implications for genome stability in somatic cells, as well as the interface between epigenetic repression and viral latency. ..
  3. Wang H, An W, Cao R, Xia L, Erdjument Bromage H, Chatton B, et al. mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression. Mol Cell. 2003;12:475-87 pubmed
    ..Previously, we reported that ESET/SETDB1 is a histone methyltransferase (HMTase)...
  4. Hong W, Li J, Wang B, Chen L, Niu W, Yao Z, et al. Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated repression of E2F1 gene expression and cell proliferation. Biochem Biophys Res Commun. 2011;415:650-5 pubmed publisher
    ..Here, we report that the histone H3 lysine 9 (H3K9) methyltransferase (HMT) ESET is an integral component of the corepressor Alien complex and the Alien/ESET complex is recruited to both sites, ..
  5. Loyola A, Tagami H, Bonaldi T, Roche D, Quivy J, Imhof A, et al. The HP1alpha-CAF1-SetDB1-containing complex provides H3K9me1 for Suv39-mediated K9me3 in pericentric heterochromatin. EMBO Rep. 2009;10:769-75 pubmed publisher
  6. Gehrig S, van der Poel C, Sayer T, Schertzer J, Henstridge D, Church J, et al. Hsp72 preserves muscle function and slows progression of severe muscular dystrophy. Nature. 2012;484:394-8 pubmed publisher
  7. Koide S, Oshima M, Takubo K, Yamazaki S, Nitta E, Saraya A, et al. Setdb1 maintains hematopoietic stem and progenitor cells by restricting the ectopic activation of nonhematopoietic genes. Blood. 2016;128:638-49 pubmed publisher
    Setdb1, also known as Eset, is a methyltransferase that catalyzes trimethylation of H3K9 (H3K9me3) and plays an essential role in the silencing of endogenous retroviral elements (ERVs) in the developing embryo and embryonic stem cells (..
  8. Jiang Y, Loh Y, Rajarajan P, Hirayama T, Liao W, Kassim B, et al. The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain. Nat Genet. 2017;49:1239-1250 pubmed publisher
    ..of megabase-scale chromosomal conformations in brain after neuronal ablation of Setdb1 (also known as Kmt1e; encodes a histone H3 lysine 9 methyltransferase), including a large topologically associated 1...
  9. An J, Zhang X, Qin J, Wan Y, Hu Y, Liu T, et al. The histone methyltransferase ESET is required for the survival of spermatogonial stem/progenitor cells in mice. Cell Death Dis. 2014;5:e1196 pubmed publisher
    ..Previous studies suggested that histone methyltransferase ERG-associated protein with SET domain (ESET) represses gene expression and is essential for the maintenance of the pool of embryonic stem cells and neurons...
  10. Jiang Y, Matevossian A, Guo Y, Akbarian S. Setdb1-mediated histone H3K9 hypermethylation in neurons worsens the neurological phenotype of Mecp2-deficient mice. Neuropharmacology. 2011;60:1088-97 pubmed publisher
    ..neuronal expression of the histone H3-lysine 9 specific methyl-transferase, Setdb1 (Set domain, bifurcated 1)/Eset/Kmt1e, which is normally present only at low levels in differentiated neurons, rescues the RTT-like phenotype of Mecp2-..
  11. Fei Q, Yang X, Jiang H, Wang Q, Yu Y, Yu Y, et al. SETDB1 modulates PRC2 activity at developmental genes independently of H3K9 trimethylation in mouse ES cells. Genome Res. 2015;25:1325-35 pubmed publisher
    ..The currently identified reciprocal action between SETDB1 and PRC2 reveals a novel mechanism underlying ES cell pluripotency and differentiation regulation. ..
  12. Li H, Rauch T, Chen Z, SZABO P, Riggs A, Pfeifer G. The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells. J Biol Chem. 2006;281:19489-500 pubmed
    ..Trimethylation of H3-K9 by the recently identified euchromatic histone methyltransferase SETDB1/ESET may be responsible for transcriptional repression of certain promoters...
  13. Cho S, Park J, Kwon S, Kang Y. Dynamics of Setdb1 expression in early mouse development. Gene Expr Patterns. 2012;12:213-8 pubmed publisher
    Setdb1/Eset, a histone lysine methyltransferase, is recruited by various transcription factors to modify local chromatin...
  14. Fisher C, Marks H, Cho L, Andrews R, Wormald S, Carroll T, et al. An efficient method for generation of bi-allelic null mutant mouse embryonic stem cells and its application for investigating epigenetic modifiers. Nucleic Acids Res. 2017;45:e174 pubmed publisher
    ..Our strategy to generate null mutant mouse ES cells is applicable to thousands of genes and repurposes existing IKMC Intermediate Vectors. ..
  15. Girardot M, Hirasawa R, Kacem S, Fritsch L, Pontis J, Kota S, et al. PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G + C-rich regions of the mouse genome. Nucleic Acids Res. 2014;42:235-48 pubmed publisher
    ..Conversely, depletion of ESET (KMT1E) or SUV420H1/H2 (KMT5B/C) affected H3K9me3 and H4K20me3, respectively, without altering H4R3me2s at ICRs...
  16. Shirato H, Ogawa S, Nakajima K, Inagawa M, Kojima M, Tachibana M, et al. A jumonji (Jarid2) protein complex represses cyclin D1 expression by methylation of histone H3-K9. J Biol Chem. 2009;284:733-9 pubmed publisher
    ..These results suggest that Jmj methylates H3-K9 and represses cyclin D1 expression through G9a and GLP, and that Jmj family proteins can regulate gene expression by not only histone demethylation but also other histone modification. ..
  17. Bassett J, Gogakos A, White J, Evans H, Jacques R, Van der Spek A, et al. Rapid-throughput skeletal phenotyping of 100 knockout mice identifies 9 new genes that determine bone strength. PLoS Genet. 2012;8:e1002858 pubmed publisher
    ..Application of the approach to diseases affecting other physiological systems will help to realize the full potential of the International Mouse Phenotyping Consortium. ..
  18. Yang L, Mei Q, Zielinska Kwiatkowska A, Matsui Y, Blackburn M, Benedetti D, et al. An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B. Biochem J. 2003;369:651-7 pubmed
    ..related gene)-associated protein with a SET (suppressor of variegation, enhancer of zest and trithorax) domain (ESET) that was found to have the activity of a histone H3-specific methyltransferase...
  19. Sridharan R, Gonzales Cope M, Chronis C, Bonora G, McKee R, Huang C, et al. Proteomic and genomic approaches reveal critical functions of H3K9 methylation and heterochromatin protein-1? in reprogramming to pluripotency. Nat Cell Biol. 2013;15:872-82 pubmed publisher
    ..Together, our findings demonstrate that Cbx3 and H3K9 methylation restrict late reprogramming events, and suggest that a marked change in global chromatin character constitutes an epigenetic roadblock for reprogramming. ..
  20. Rowe H, Friedli M, Offner S, Verp S, Mesnard D, Marquis J, et al. De novo DNA methylation of endogenous retroviruses is shaped by KRAB-ZFPs/KAP1 and ESET. Development. 2013;140:519-29 pubmed publisher
    ..because of its previously defined role in maintaining the silencing of ERVs through the histone methyltransferase ESET and histone H3 lysine 9 trimethylation...
  21. Daxinger L, Oey H, Isbel L, Whitelaw N, Youngson N, Spurling A, et al. Hypomethylation of ERVs in the sperm of mice haploinsufficient for the histone methyltransferase Setdb1 correlates with a paternal effect on phenotype. Sci Rep. 2016;6:25004 pubmed publisher
    ..Our results identify Setdb1 as a paternal effect gene in the mouse and suggest that epigenetic inheritance may be more likely in individuals with altered levels of epigenetic modifiers. ..
  22. Kim J, Zhao H, Dan J, Kim S, Hardikar S, Hollowell D, et al. Maternal Setdb1 Is Required for Meiotic Progression and Preimplantation Development in Mouse. PLoS Genet. 2016;12:e1005970 pubmed publisher
    ..Our results uncover an important link between the epigenetic machinery and the major signaling pathway governing meiotic progression. ..
  23. Fei Q, Shang K, Zhang J, Chuai S, Kong D, Zhou T, et al. Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53. Nat Commun. 2015;6:8651 pubmed publisher
    ..Together, we provide both genetic and biochemical evidence for a mechanism by which SETDB1 regulates cancer cell growth via methylation of p53. ..
  24. Yang L, Lawson K, Teteak C, Zou J, Hacquebord J, Patterson D, et al. ESET histone methyltransferase is essential to hypertrophic differentiation of growth plate chondrocytes and formation of epiphyseal plates. Dev Biol. 2013;380:99-110 pubmed publisher
    The ESET (also called SETDB1) protein contains an N-terminal tudor domain that mediates protein-protein interactions and a C-terminal SET domain that catalyzes methylation of histone H3 at lysine 9...
  25. Yahiro K, Higashihori N, Moriyama K. Histone methyltransferase Setdb1 is indispensable for Meckel's cartilage development. Biochem Biophys Res Commun. 2017;482:883-888 pubmed publisher
    ..Overall, to our knowledge, the present study is the first to show that epigenetic regulation by Setdb1 is indispensable for the embryonic development of Meckel's cartilage. ..
  26. Takikita S, Muro R, Takai T, Otsubo T, Kawamura Y, Dohi T, et al. A Histone Methyltransferase ESET Is Critical for T Cell Development. J Immunol. 2016;197:2269-79 pubmed publisher
    b>ESET/SETDB1, one of the major histone methyltransferases, catalyzes histone 3 lysine 9 (H3K9) trimethylation...
  27. Sun L, Fang J. E3-Independent Constitutive Monoubiquitination Complements Histone Methyltransferase Activity of SETDB1. Mol Cell. 2016;62:958-966 pubmed publisher
    ..Together, our findings highlight an E3-independent mechanism for monoubiquitination and reveal mechanistic details of SETDB1's enzymatic activity and the functional significance of its SET-Insertion. ..
  28. Liu T, Chen X, Li T, Li X, Lyu Y, Fan X, et al. Histone methyltransferase SETDB1 maintains survival of mouse spermatogonial stem/progenitor cells via PTEN/AKT/FOXO1 pathway. Biochim Biophys Acta Gene Regul Mech. 2017;1860:1094-1102 pubmed publisher
    ..This study replenishes the research on the epigenetic regulation of SSC survival, and provides a new insight for the future study of epigenetic regulation of spermatogenesis. ..
  29. Thompson P, Dulberg V, Moon K, Foster L, Chen C, Karimi M, et al. hnRNP K coordinates transcriptional silencing by SETDB1 in embryonic stem cells. PLoS Genet. 2015;11:e1004933 pubmed publisher
    ..Taken together, these findings reveal a novel regulatory hierarchy governing SETDB1 recruitment and in turn, transcriptional silencing in mESCs. ..
  30. Sampath Kumar A, Seah M, Ling K, Wang Y, Tan J, Nitsch S, et al. Loss of maternal Trim28 causes male-predominant early embryonic lethality. Genes Dev. 2017;31:12-17 pubmed publisher
    ..Rbmy1a1 is a novel target of the TRIM28 complex, which is required to protect its repressive epigenetic state during embryonic epigenetic reprogramming. ..
  31. Ideno H, Shimada A, Imaizumi K, Kimura H, Abe M, Nakashima K, et al. Predominant expression of H3K9 methyltransferases in prehypertrophic and hypertrophic chondrocytes during mouse growth plate cartilage development. Gene Expr Patterns. 2013;13:84-90 pubmed publisher
  32. Sharif J, Endo T, Nakayama M, Karimi M, Shimada M, Katsuyama K, et al. Activation of Endogenous Retroviruses in Dnmt1(-/-) ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA. Cell Stem Cell. 2016;19:81-94 pubmed publisher
    ..Thus, our observations reveal an unexpected antagonistic interplay between two repressive pathways involved in retroviral silencing in mammalian cells. ..
  33. Lee J, Hagerty S, Cormier K, Kim J, Kung A, Ferrante R, et al. Monoallele deletion of CBP leads to pericentromeric heterochromatin condensation through ESET expression and histone H3 (K9) methylation. Hum Mol Genet. 2008;17:1774-82 pubmed publisher
    ..deletion of CREB binding protein (CBP) results in the induction of ERG-associated protein with SET domain (ESET) and increases trimethylation of histone H3 (K9) and condensation of pericentromeric heterochromatin structure in ..
  34. Cho S, Park J, Kang Y. Dual functions of histone-lysine N-methyltransferase Setdb1 protein at promyelocytic leukemia-nuclear body (PML-NB): maintaining PML-NB structure and regulating the expression of its associated genes. J Biol Chem. 2011;286:41115-24 pubmed publisher
    Setdb1/Eset is a histone H3 lysine 9 (H3K9)-specific methyltransferase that associates with various transcription factors to regulate gene expression via chromatin remodeling...
  35. Benlhabib H, Mendelson C. Epigenetic regulation of surfactant protein A gene (SP-A) expression in fetal lung reveals a critical role for Suv39h methyltransferases during development and hypoxia. Mol Cell Biol. 2011;31:1949-58 pubmed publisher
  36. Jiang Y, Jakovcevski M, Bharadwaj R, Connor C, Schroeder F, Lin C, et al. Setdb1 histone methyltransferase regulates mood-related behaviors and expression of the NMDA receptor subunit NR2B. J Neurosci. 2010;30:7152-67 pubmed publisher
    ..methyltransferases specific for the histone H3-lysine 9 residue, including Setdb1 (Set domain, bifurcated 1)/Eset/Kmt1e are associated with repressive chromatin remodeling and expressed in adult brain, but potential effects on ..
  37. Pasquarella A, Ebert A, Pereira de Almeida G, Hinterberger M, Kazerani M, Nuber A, et al. Retrotransposon derepression leads to activation of the unfolded protein response and apoptosis in pro-B cells. Development. 2016;143:1788-99 pubmed publisher
    ..Production of MLV proteins leads to activation of the unfolded protein response pathway and apoptosis. Thus, our data demonstrate that B cell development depends on the proper repression of retrotransposon sequences through Setdb1. ..
  38. Eymery A, Liu Z, Ozonov E, Stadler M, Peters A. The methyltransferase Setdb1 is essential for meiosis and mitosis in mouse oocytes and early embryos. Development. 2016;143:2767-79 pubmed publisher
    ..Our results identify Setdb1 as a newly discovered meiotic and embryonic competence factor safeguarding genome integrity at the onset of life. ..
  39. Daxinger L, Harten S, Oey H, Epp T, Isbel L, Huang E, et al. An ENU mutagenesis screen identifies novel and known genes involved in epigenetic processes in the mouse. Genome Biol. 2013;14:R96 pubmed
    ..Overall, the Momme collection of mouse mutants provides a valuable resource for researchers across many disciplines. ..
  40. Ryu H, Lee J, Hagerty S, Soh B, McAlpin S, Cormier K, et al. ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington's disease. Proc Natl Acad Sci U S A. 2006;103:19176-81 pubmed
    ..ERG-associated protein with SET domain (ESET), a histone H3 (K9) methyltransferase, mediates histone methylation...
  41. Blackburn M, Chansky H, Zielinska Kwiatkowska A, Matsui Y, Yang L. Genomic structure and expression of the mouse ESET gene encoding an ERG-associated histone methyltransferase with a SET domain. Biochim Biophys Acta. 2003;1629:8-14 pubmed
    b>ESET (ERG-associated protein with a SET domain, also called SETDB1) is a novel histone methyltransferase that catalyzes methylation of histone H3-lysine 9 (H3-K9)...
  42. Mysliwiec M, Carlson C, Tietjen J, Hung H, Ansari A, Lee Y. Jarid2 (Jumonji, AT rich interactive domain 2) regulates NOTCH1 expression via histone modification in the developing heart. J Biol Chem. 2012;287:1235-41 pubmed publisher
    ..Therefore, our study provides new mechanistic insights into epigenetic regulation by Jarid2, which will enhance our understanding of the molecular basis of other organ development and biological processes. ..
  43. Kera Y, Katoh Y, Ohta M, Matsumoto M, Takano Yamamoto T, Igarashi K. Methionine adenosyltransferase II-dependent histone H3K9 methylation at the COX-2 gene locus. J Biol Chem. 2013;288:13592-601 pubmed publisher
    ..We discuss both gene-specific and epigenome-wide functions of MATII?. ..
  44. Lawson K, Teteak C, Zou J, Hacquebord J, Ghatan A, Zielinska Kwiatkowska A, et al. Mesenchyme-specific knockout of ESET histone methyltransferase causes ectopic hypertrophy and terminal differentiation of articular chondrocytes. J Biol Chem. 2013;288:32119-25 pubmed publisher
    ..In this study, we have found that ESET (an ERG-associated protein with a SET domain, also called SETDB1) histone methyltransferase is expressed in ..
  45. Cho S, Park J, Kang Y. Regulated nuclear entry of over-expressed Setdb1. Genes Cells. 2013;18:694-703 pubmed publisher