General Information of the Ferroptosis Regulator (ID: REG10029)
Regulator Name Histone-lysine N-methyltransferase SUV39H1 (SUV39H1)
Synonyms
KMT1A, SUV39H; Histone H3-K9 methyltransferase 1; Lysine N-methyltransferase 1A; Position-effect variegation 3-9 homolog; Suppressor of variegation 3-9 homolog 1
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Gene Name SUV39H1
Gene ID 6839
Regulator Type Protein coding
Uniprot ID O43463
Sequence
MAENLKGCSVCCKSSWNQLQDLCRLAKLSCPALGISKRNLYDFEVEYLCDYKKIREQEYY
LVKWRGYPDSESTWEPRQNLKCVRILKQFHKDLERELLRRHHRSKTPRHLDPSLANYLVQ
KAKQRRALRRWEQELNAKRSHLGRITVENEVDLDGPPRAFVYINEYRVGEGITLNQVAVG
CECQDCLWAPTGGCCPGASLHKFAYNDQGQVRLRAGLPIYECNSRCRCGYDCPNRVVQKG
IRYDLCIFRTDDGRGWGVRTLEKIRKNSFVMEYVGEIITSEEAERRGQIYDRQGATYLFD
LDYVEDVYTVDAAYYGNISHFVNHSCDPNLQVYNVFIDNLDERLPRIAFFATRTIRAGEE
LTFDYNMQVDPVDMESTRMDSNFGLAGLPGSPKKRVRIECKCGTESCRKYLF

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Family Histone-lysine methyltransferase family
Function
Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. Also weakly methylates histone H1 (in vitro). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.

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HGNC ID
HGNC:11479
KEGG ID hsa:6839
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
SUV39H1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
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Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Hereditary Leiomyomatosis ICD-11: 2C90
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell cycle
In Vitro Model
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
Caki-1 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0234
A-498 cells Renal cell carcinoma Homo sapiens CVCL_1056
769-P cells Renal cell carcinom Homo sapiens CVCL_1050
ACHN cells Papillary renal cell carcinoma Homo sapiens CVCL_1067
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Female SCID mice (4-6 weeks old) were purchased and used for the xenograft models. Approximately 5 x 106 ccRCC cells were injected subcutaneously into the flank. The mice were treated with vehicle (control) or chaetocin (0.5 mg/kg/day) by daily intraperitoneal injection.

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Response regulation SUV39H1 expression is frequently upregulated in clear cell renal cell carcinoma (ccRCC) tumors and is significantly correlated with ccRCC progression. Function loss of SUV39H1 in ccRCC tumors contributes the hypomethylation of the DPP4 promoter to upregulate DPP4 expression and induces DPP4-mediated ferroptosis to suppress cell proliferation.
Hereditary Leiomyomatosis [ICD-11: 2C90]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Histone-lysine N-methyltransferase SUV39H1 (SUV39H1) Protein coding
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell cycle
In Vitro Model
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
Caki-1 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0234
A-498 cells Renal cell carcinoma Homo sapiens CVCL_1056
769-P cells Renal cell carcinom Homo sapiens CVCL_1050
ACHN cells Papillary renal cell carcinoma Homo sapiens CVCL_1067
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Female SCID mice (4-6 weeks old) were purchased and used for the xenograft models. Approximately 5 x 106 ccRCC cells were injected subcutaneously into the flank. The mice were treated with vehicle (control) or chaetocin (0.5 mg/kg/day) by daily intraperitoneal injection.

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Response regulation SUV39H1 expression is frequently upregulated in clear cell renal cell carcinoma (ccRCC) tumors and is significantly correlated with ccRCC progression. Function loss of SUV39H1 in ccRCC tumors contributes the hypomethylation of the DPP4 promoter to upregulate DPP4 expression and induces DPP4-mediated ferroptosis to suppress cell proliferation.
References
Ref 1 SUV39H1 deficiency suppresses clear cell renal cell carcinoma growth by inducing ferroptosis. Acta Pharm Sin B. 2021 Feb;11(2):406-419. doi: 10.1016/j.apsb.2020.09.015. Epub 2020 Sep 30.