Molecule Information

General Information of the Molecule (ID: Mol04409)

• Name: Histone-lysine N-methyltransferase EZH2 (EZH2) ,Homo sapiens
• Synonyms: ENX-1; Enhancer of zeste homolog 2 ; Lysine N-methyltransferase 6
• Molecule Type: Protein
• Gene Name: EZH2
• Gene ID: 2146
• Sequence:
  MGQTGKKSEKGPVCWRKRVKSEYMRLRQLKRFRRADEVKSMFSSNRQKILERTEILNQEW
  KQRRIQPVHILTSVSSLRGTRECSVTSDLDFPTQVIPLKTLNAVASVPIMYSWSPLQQN
  F MVEDETVLHNIPYMGDEVLDQDGTFIEELIKNYDGKVHGDRECGFINDEIFVELVNAL
  GQ YNDDDDDDDGDDPEEREEKQKDLEDHRDDKESRPPRKFPSDKIFEAISSMFPDKGTA
  EEL KEKYKELTEQQLPGALPPECTPNIDGPNAKSVQREQSLHSFHTLFCRRCFKYDCFL
  HPFH ATPNTYKRKNTETALDNKPCGPQCYQHLEGAKEFAAALTAERIKTPPKRPGGRRR
  GRLPN NSSRPSTPTINVLESKDTDSDREAGTETGGENNDKEEEEKKDETSSSSEANSRC
  QTPIKM KPNIEPPENVEWSGAEASMFRVLIGTYYDNFCAIARLIGTKTCRQVYEFRVKE
  SSIIAPA PAEDVDTPPRKKKRKHRLWAAHCRKIQLKKDGSSNHVYNYQPCDHPRQPCDS
  SCPCVIAQ NFCEKFCQCSSECQNRFPGCRCKAQCNTKQCPCYLAVRECDPDLCLTCGAA
  DHWDSKNVS CKNCSIQRGSKKHLLLAPSDVAGWGIFIKDPVQKNEFISEYCGEIISQDE
  ADRRGKVYDK YMCSFLFNLNNDFVVDATRKGNKIRFANHSVNPNCYAKVMMVNGDHRIG
  IFAKRAIQTGE ELFFDYRYSQADALKYVGIEREMEIP
• Function: Polycomb group protein. Catalytic subunit of thePRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of theaffected target gene. Able to mono-, di- and trimethylate 'Lys-27' ofhistone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively.Displays a preference for substrates with less methylation, losesactivity when progressively more methyl groups are incorporated intoH3K27, H3K27me0 > H3K27me1 > H3K27me2 . Compared to EZH1-containing complexes, it is moreabundant in embryonic stem cells and plays a major role in formingH3K27me3, which is required for embryonic stem cell identity and properdifferentiation. The PRC2/EED-EZH2 complex may also serve as arecruiting platform for DNA methyltransferases, thereby linking twoepigenetic repression systems. Genes repressed by the PRC2/EED-EZH2complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid targetgenes. EZH2 can also methylate non-histone proteins such as thetranscription factor GATA4 and the nuclear receptor RORA. Regulates thecircadian clock via histone methylation at the promoter of thecircadian genes. Essential for the CRY1/2-mediated repression of thetranscriptional activation of PER1/2 by the CLOCK-BMAL1 heterodimer;involved in the di and trimethylation of 'Lys-27' of histone H3 onPER1/2 promoters which is necessary for the CRY1/2 proteins to inhibittranscription. {ECO:0000269|PubMed:14532106,ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737,ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16179254,ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:16618801,ECO:0000269|PubMed:16717091, ECO:0000269|PubMed:16936726,ECO:0000269|PubMed:17210787, ECO:0000269|PubMed:17344414,ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:19026781,ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:22323599,ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:24474760,ECO:0000269|PubMed:30026490, ECO:0000269|PubMed:30923826}.
• Uniprot ID: EZH2_HUMAN
• Ensembl ID: ENSG0000010646212
• HGNC ID: HGNC:3527

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Melanoma [ICD-11: 2C30.0] [1]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Methylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: B16-BL6 cells; Skin; Homo sapiens (Human); CVCL_0157
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a histone methyltransferase EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of histone methylation induced under hypoxic tumor microenvironment.

Disease Class: Melanoma [ICD-11: 2C30.0] [1]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Methylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Colon-26 carcinoma cells; Skin; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a histone methyltransferase EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of histone methylation induced under hypoxic tumor microenvironment.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Melanoma [ICD-11: 2C30.0] [1]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Methylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: B16-BL6 cells; Skin; Homo sapiens (Human); CVCL_0157
• In Vitro Model: Colon-26 carcinoma cells; Skin; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a histone methyltransferase EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of histone methylation induced under hypoxic tumor microenvironment.

Paclitaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Melanoma [ICD-11: 2C30.0] [1]

• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Methylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: B16-BL6 cells; Skin; Homo sapiens (Human); CVCL_0157
• In Vitro Model: Colon-26 carcinoma cells; Skin; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a histone methyltransferase EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of histone methylation induced under hypoxic tumor microenvironment.

Investigative Drug(s) 1 drug(s) in total

3-Deazaneplanocin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Melanoma [ICD-11: 2C30.0] [1]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Sensitive Drug: 3-Deazaneplanocin
• Molecule Alteration: Methylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Colon-26 carcinoma cells; Skin; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a histone methyltransferase EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of histone methylation induced under hypoxic tumor microenvironment.

Disease Class: Melanoma [ICD-11: 2C30.0] [1]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Sensitive Drug: 3-Deazaneplanocin
• Molecule Alteration: Methylation; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: B16-BL6 cells; Skin; Homo sapiens (Human); CVCL_0157
• Experiment for Molecule Alteration: Western blot assay
• Experiment for Drug Resistance: WST-8 assay
• Mechanism Description: These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a histone methyltransferase EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of histone methylation induced under hypoxic tumor microenvironment.

References

• Ref 1: 3-deazaneplanocin A, a histone methyltransferase inhibitor, improved the chemoresistance induced under hypoxia in melanoma cells. Biochem Biophys Res Commun. 2023 Oct 15;677:26-30.