SETDB1 explained

Histone-lysine N-methyltransferase SETDB1 is an enzyme that in humans is encoded by the SETDB1 gene.^{[1] [2]} SETDB1 is also known as KMT1E or H3K9 methyltransferase ESET.

Function

The SET domain is a highly conserved, approximately 150-amino acid motif implicated in the modulation of chromatin structure. It was originally identified as part of a larger conserved region present in the Drosophila Trithorax protein and was subsequently identified in the Drosophila Su(var)3-9 and 'Enhancer of zeste' proteins, from which the acronym SET is derived. Studies have suggested that the SET domain may be a signature of proteins that modulate transcriptionally active or repressed chromatin states through chromatin remodeling activities.

Interactions

SETDB1 has been shown to interact with TRIM28.^[3] >

See also

• SETD1A, a protein that is highly homologous to SETDB1

Further reading

• Nomura N, Nagase T, Miyajima N, Sazuka T, Tanaka A, Sato S, Seki N, Kawarabayasi Y, Ishikawa K, Tabata S . Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1 . DNA Res. . 1 . 5 . 223–9 . 1994 . 7584044 . 10.1093/dnares/1.5.223 . free .
• Yang L, Xia L, Wu DY, Wang H, Chansky HA, Schubach WH, Hickstein DD, Zhang Y . Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor . Oncogene . 21 . 1 . 148–52 . 2002 . 11791185 . 10.1038/sj.onc.1204998 . 10912876 .
• Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ . SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins . Genes Dev. . 16 . 8 . 919–32 . 2002 . 11959841 . 152359 . 10.1101/gad.973302 .
• Yang L, Mei Q, Zielinska-Kwiatkowska A, Matsui Y, Blackburn ML, Benedetti D, Krumm AA, Taborsky GJ, Chansky HA . An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B . Biochem. J. . 369 . Pt 3 . 651–7 . 2003 . 12398767 . 1223118 . 10.1042/BJ20020854 .
• Nakayama M, Kikuno R, Ohara O . Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs . Genome Res. . 12 . 11 . 1773–84 . 2002 . 12421765 . 187542 . 10.1101/gr.406902 .
• Ayyanathan K, Lechner MS, Bell P, Maul GG, Schultz DC, Yamada Y, Tanaka K, Torigoe K, Rauscher FJ . Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation . Genes Dev. . 17 . 15 . 1855–69 . 2003 . 12869583 . 196232 . 10.1101/gad.1102803 .
• Wang H, An W, Cao R, Xia L, Erdjument-Bromage H, Chatton B, Tempst P, Roeder RG, Zhang Y . mAM facilitates conversion by ESET of dimethyl to trimethyl lysine 9 of histone H3 to cause transcriptional repression . Mol. Cell . 12 . 2 . 475–87 . 2003 . 14536086 . 10.1016/j.molcel.2003.08.007 . free .
• Paces-Fessy M, Boucher D, Petit E, Paute-Briand S, Blanchet-Tournier MF . The negative regulator of Gli, Suppressor of fused (Sufu), interacts with SAP18, Galectin3 and other nuclear proteins . Biochem. J. . 378 . Pt 2 . 353–62 . 2004 . 14611647 . 1223961 . 10.1042/BJ20030786 .
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM . Functional proteomics mapping of a human signaling pathway . Genome Res. . 14 . 7 . 1324–32 . 2004 . 15231748 . 442148 . 10.1101/gr.2334104 .
• Bernhard Landwehrmeyer . Goehler H, Lalowski M, Stelzl U, Waelter S, Stroedicke M, Worm U, Droege A, Lindenberg KS, Knoblich M, Haenig C, Herbst M, Suopanki J, Scherzinger E, Abraham C, Bauer B, Hasenbank R, Fritzsche A, Ludewig AH, Büssow K, Buessow K, Coleman SH, Gutekunst CA, Landwehrmeyer BG, Lehrach H, Wanker EE . A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease . Mol. Cell . 15 . 6 . 853–65 . 2004 . 15383276 . 10.1016/j.molcel.2004.09.016 . free .
• Ichimura T, Watanabe S, Sakamoto Y, Aoto T, Fujita N, Nakao M . Transcriptional repression and heterochromatin formation by MBD1 and MCAF/AM family proteins . J. Biol. Chem. . 280 . 14 . 13928–35 . 2005 . 15691849 . 10.1074/jbc.M413654200 . free .
• Verschure PJ, van der Kraan I, de Leeuw W, van der Vlag J, Carpenter AE, Belmont AS, van Driel R . In vivo HP1 targeting causes large-scale chromatin condensation and enhanced histone lysine methylation . Mol. Cell. Biol. . 25 . 11 . 4552–64 . 2005 . 15899859 . 1140641 . 10.1128/MCB.25.11.4552-4564.2005 .
• Gevaert K, Staes A, Van Damme J, De Groot S, Hugelier K, Demol H, Martens L, Goethals M, Vandekerckhove J . Global phosphoproteome analysis on human HepG2 hepatocytes using reversed-phase diagonal LC . Proteomics . 5 . 14 . 3589–99 . 2005 . 16097034 . 10.1002/pmic.200401217 . 895879 .
• Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Orouji E, Federico A, Larribere L, Novak D, Lipka DB, Assenov Y, Sachindra S, Hueser L, Granados K, Gebhardt C, Plass C, Umansky V, Utikal J . Histone methyltransferase SETDB1 contributes to melanoma tumorigenesis and serves as a new potential therapeutic target . Int J Cancer . 12 . 3462–3477 . 2019 . 145 . 31131878 . 10.1002/ijc.32432 . free .
• Strepkos D, Markouli M, Klonou A, Papavassiliou AG, Piperi C . Histone methyltransferase SETDB1: A common denominator of tumorigenesis with therapeutic potential . Cancer Research . 81 . 3 . 525–534 . 2021 . 33115801 . 10.1158/0008-5472.CAN-20-2906 . 226046421 . free .
• Cao N, Yu Y, Zhu H, Chen M, Chen P, Zhuo M, Ye M . SETDB1 promotes the progression of colorectal cancer via epigenetically silencing p21 expression. . Cell Death & Disease . 11 . 5 . 2020 . 351 . 32393761 . 7214465 . 10.1038/s41419-020-2561-6 .
• Lee S, Lee C, Hwang CY, Kim D, Han Y, Hong SN, Cho KH . Network inference analysis identifies SETDB1 as a key regulator for reverting colorectal cancer cells into differentiated normal-like cells . Molecular Cancer Research . 18 . 1 . 118–129 . 2020 . 31896605 . 10.1158/1541-7786.MCR-19-0450 . free .
• Fukuda K, Shinkai Y . SETDB1-Mediated silencing of retroelements . Viruses . 12 . 6 . 596 . 2020 . 32486217 . 7354471 . 10.3390/v12060596 . free .

Notes and References

1. Harte PJ, Wu W, Carrasquillo MM, Matera AG . Assignment of a novel bifurcated SET domain gene, SETDB1, to human chromosome band 1q21 by in situ hybridization and radiation hybrids . Cytogenet. Cell Genet. . 84 . 1–2 . 83–6 . June 1999 . 10343109 . 10.1159/000015220 . 10805552 .
2. Web site: Entrez Gene: SETDB1 SET domain, bifurcated 1.
3. Schultz DC, Ayyanathan K, Negorev D, Maul GG, Rauscher FJ . SETDB1: a novel KAP-1-associated histone H3, lysine 9-specific methyltransferase that contributes to HP1-mediated silencing of euchromatic genes by KRAB zinc-finger proteins . Genes Dev. . 16 . 8 . 919–32 . April 2002 . 11959841 . 152359 . 10.1101/gad.973302 .