title: Inhibition of euchromatic histone methyltransferase 1 and 2 sensitizes chronic myeloid leukemia cells to interferon treatment.
abstract: BACKGROUND
  H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the type I interferon response.
  
  
  RESULTS
  We report the application of EHMT1 and EHMT2 specific chemical inhibitors to sensitize CML cell lines to interferon and imatinib treatments. Inhibition of EHMT1 and EHMT2 with BIX01294 enhances the cytotoxicity of IFNα2a in four CML cell lines, K562, KCL22, BV173 and KT1 cells. Chromatin immunoprecipitation assay shows that BIX01294 treatment enhances type I interferon response by reducing H3K9me2 at the promoters of interferon-stimulated genes. Additionally, BIX01294 treatment augments IFNα2a- and imatinib-mediated apoptosis in CML cell lines. Moreover, our data suggest that the expression level of EHMT1 and EHMT2 inversely correlates with the type I interferon responsiveness in CML cell lines.
  
  
  CONCLUSIONS
  Our study sheds light on the role of EHMT1 and EHMT2 as potential targets in improving the efficacy of standard treatments of CML.
authors: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Sheng Wei
authors: SW
authors: Loh
authors: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Wei Lun
authors: WL
authors: Ng
authors: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Kok Siong
authors: KS
authors: Yeo
authors: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Yat-Yuen
authors: YY
authors: Lim
authors: Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors: Chee-Kwee
authors: CK
authors: Ea
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001381:Azepines / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006649:Histocompatibility Antigens / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D007370:Interferon Type I / Q000494:pharmacology*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001381:Azepines; C518299:BIX 01294; D001549:Benzamides; D006649:Histocompatibility Antigens; D007370:Interferon Type I; D010879:Piperazines; D011743:Pyrimidines; D011799:Quinazolines; C561310:UNC 0638; D000068877:Imatinib Mesylate; C455847:EHMT1 protein, human; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase