CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

SETDB1ESET; KG1T; KMT1E; H3-K9-HMTase4; KIAA0067

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

H3K9me3

Introduction

Full Name: SET domain, bifurcated 1 . SETDB1 is a histone H3K9-specific methyltransferase. This enzyme is involved in transcriptional regulation, stem cell differentiation, proviral silencing, early development, tumorigenesis, DNA replication, and chromatin assembly, and it controls the G1/S transition of the cell cycle and thyroid hormone-repressed proliferation (1-7).

Function and Interaction

SETDB1 is capable of promoting HP1 binding through its methyltransferase function, and it contributes to the HP1-mediated silencing of euchromatic genes (8). SETDB1 and the CHD3/Mi2 component of the NuRD complex are recruited by KAP1 sumoylation, thus silencing KAP-1 target genes (9). SETDB1 interacts with Alien and is recruited to the hormone response element region of the promoters of TRβ1 target genes, thus forming the Alien/ESET complex and suppressing the transcription of TRβ1 target genes (2). SETDB1 is thought to associate with the histone deacetylases HDAC1 and HDAC2 and transcriptional co-repressors mSin3A and mSin3B, thereby forming a complex involved in multiple transcriptional repression pathways (10). SETDB1 participates in both maintaining the structural integrity of promyelocytic leukemia-nuclear bodies (PML-NBs) and modulating the transcription of PML-NB-associated genes (11). SETDB1 also interacts with the ets-related transcription factors ERG, MBD, CAF-1, and Sp3 (1,3,12). SETDB1 plays a key role in suppressing aberrant gene transcription by repressing the expression of proximal ERVs (endogenous retroviruses) (13).

Disease Association

SETDB1 is believed to promote dramatic melanoma formation in zebrafish and is suggested to be an oncogene involved in melanoma (6). Overexpression of SETDB1 in adult forebrain neurons results in antidepressant-like phenotypes in behavioral paradigms of anhedonia, despair, and learned helplessness, indicating that SETDB1 acts a modulator of mood-related behaviors (14).

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Homo sapiensWM853.2Melanoma CellNAGSE36579 ,GSM897123
Click  DownloadNANA

ChIP-Seq data of related histone modifications


Products/SubstratesSpeciesCell lineCell typeTissueDataDownload Send to CistromeAnalysis FiguresReference
H3K9me3 Mus musculus 3T3-L1 Preadipocyte Adipose GSE58491 ,GSM1412500 Bed     Big wiggle
Click   Download25503565
H3K9me3 Homo sapiens U2OS None Bone GSE68129 ,GSM1664370 Bed     Big wiggle
Click   Download25922909
H3K9me3 Mus musculus 3T3-L1 Preadipocyte Adipose GSE73434 ,GSM1893625 Bed     Big wiggle
Click   Download26590716
H3K9me3 Mus musculus 3T3-L1 Preadipocyte Adipose GSE73434 ,GSM1893639 Bed     Big wiggle
Click   Download26590716
H3K9me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE17642 ,GSM440257 Bed     Big wiggle
Click   Download19884257
H3K9me3 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE18371 ,GSM459278 Bed     Big wiggle
Click   Download19884255
H3K9me3 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE18371 ,GSM459281 Bed     Big wiggle
Click   Download19884255
H3K9me3 Mus musculus V6.5 Embryonic Stem Cell Embryo GSE18371 ,GSM459282 Bed     Big wiggle
Click   Download19884255
H3K9me3 Homo sapiens K562 Erythroblast Bone Marrow GSE28162 ,GSM607493 Bed     Big wiggle
Click   Download21596310
H3K9me3 Homo sapiens K562 Erythroblast Bone Marrow GSE24632 ,GSM607494 Bed     Big wiggle
Click   Download21170338
H3K9me3 Homo sapiens WM451-lu Melanocyte Skin GSE28170 ,GSM697627 Bed     Big wiggle
Click   Download21430779
H3K9me3 Homo sapiens WM262 Melanocyte Skin GSE28170 ,GSM697628 Bed     Big wiggle
Click   Download21430779
H3K9me3 Homo sapiens K562 Erythroblast Bone Marrow GSE29611 ,GSM733776 Bed     Big wiggle
Click   Download22955616
H3K9me3 Homo sapiens U2OS NA Bone GSE31755 ,GSM788078 Bed     Big wiggle
Click   DownloadNA
H3K9me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE23943 ,GSM850407 Bed     Big wiggle
Click   Download22541430
H3K9me3 Mus musculus E14 Embryonic Stem Cell Embryo GSE36114 ,GSM881363 Bed     Big wiggle
Click   Download22682255

Notice: For bigwiggle or bed file download, if the browser cannot automatically download the file, users can right click the hyperlink and then click the "Save link as..." button, which will automatically redirect to download dialogue box, or click the "Copy link address" button and access the website in a new tab page. For data analysis in Cistrome, users should first login into the Cistrome website, then press the "Send Bed" or "Send Big wiggle" button. For data download by Cistrome, users can follow this tutorial.

References

1. Yang, L., Xia, L., Wu, D.Y., Wang, H.B., Chansky, H.A., Schubach, W.H., Hickstein, D.D. and Zhang, Y. (2002) Molecular cloning of ESET, a novel histone H3-specific methyltransferase that interacts with ERG transcription factor. Oncogene, 21, 148-152.
2. Hong, W., Li, J.R., Wang, B., Chen, L.F., Niu, W.Y., Yao, Z. and Baniahmad, A. (2011) Epigenetic involvement of Alien/ESET complex in thyroid hormone-mediated repression of E2F1 gene expression and cell proliferation. Biochem Bioph Res Co, 415, 650-655.
3. Sarraf, S.A. and Stancheva, I. (2004) Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Mol Cell, 15, 595-605.
4. Yoon, J., Lee, K.S., Park, J.S., Yu, K., Paik, S.G. and Kang, Y.K. (2008) dSETDB1 and SU(VAR)3-9 Sequentially Function during Germline-Stem Cell Differentiation in Drosophila melanogaster. PLoS One, 3.
5. Dodge, J.E., Kang, Y.K., Beppu, H., Lei, H. and Li, E. (2004) Histone H3-K9 methyltransferase ESET is essential for early development. Mol Cell Biol, 24, 2478-2486.
6. Ceol, C.J., Houvras, Y., Jane-Valbuena, J., Bilodeau, S., Orlando, D.A., Battisti, V., Fritsch, L., Lin, W.M., Hollmann, T.J., Ferre, F. et al. (2011) The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset. Nature, 471, 513-+.
7. Matsui, T., Leung, D., Miyashita, H., Maksakova, I.A., Miyachi, H., Kimura, H., Tachibana, M., Lorincz, M.C. and Shinkai, Y. (2010) Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET. Nature, 464, 927-U149.
8. Schultz, D.C., Ayyanathan, K., Negorev, D., Maul, G.G. and Rauscher, F.J. (2002) 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. Gene Dev, 16, 919-932.
9. Ivanov, A.V., Peng, H.Z., Yurchenko, V., Yap, K.L., Negorev, D.G., Schultz, D.C., Psulkowski, E., Fredericks, W.J., White, D.E., Maul, G.G. et al. (2007) PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing. Mol Cell, 28, 823-837.
10. Yang, L., Mei, Q., Zielinska-Kwiatkowska, A., Matsui, Y., Blackburn, M.L., Benedetti, D., Krumm, A.A., Taborsky, G.J., Jr. and Chansky, H.A. (2003) An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B. Biochem J, 369, 651-657.
11. Cho, S., Park, J.S. and Kang, Y.K. (2011) 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, 286, 41115-41124.
12. Stielow, B., Sapetschnig, A., Wink, C., Kruger, I. and Suske, G. (2008) SUMO-modified Sp3 represses transcription by provoking local heterochromatic gene silencing. Embo Rep, 9, 899-906.
13. Karimi, M.M., Goyal, P., Maksakova, I.A., Bilenky, M., Leung, D., Tang, J.X., Shinkai, Y., Mager, D.L., Jones, S., Hirst, M. et al. (2011) DNA Methylation and SETDB1/H3K9me3 Regulate Predominantly Distinct Sets of Genes, Retroelements, and Chimeric Transcripts in mESCs. Cell Stem Cell, 8, 676-687.
14. Jiang, Y., Jakovcevski, M., Bharadwaj, R., Connor, C., Schroeder, F.A., Lin, C.L., Straubhaar, J., Martin, G. and Akbarian, S. (2010) Setdb1 Histone Methyltransferase Regulates Mood-Related Behaviors and Expression of the NMDA Receptor Subunit NR2B. J Neurosci, 30, 7152-7167.

Figure Gallery

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About Chromatin Regulator

Chromatin Regulator Cistrome
is a unique database integrating curated information of CRs, CR ChIP-seq datasets, CR related HM ChIP-seq datasets, and analysis of the relationship between CRs and HMs ChIP-seq pairs in human and mouse.

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