Trichostatin A down-regulate DNA methyltransferase 1 in Jurkat T cells.
Histone deacetylase inhibitor Trichostatin A (TSA), alone, is able to activate the transcription of DNA methylation-mediated silenced genes in human cancer cells. Increase in expression and half-life of the DNA methyltransferase DNMT1 has been found in carcinomas of the colon, lung, liver, prostate, and breast cancer. This overexpression of DNMT1 is responsible for hypermethylation of regulatory sequences of many genes involved in tumorigenesis. Using quantitative real-time PCR and Western blot analysis, we found that TSA down-regulate DNMT1 mRNA and protein expression in Jurkat T leukemia cells clone E6-1. We also observed that TSA decreased DNMT1 mRNA stability and reduced this transcript half-life from approximately 7 to 2h. We also found that protein biosynthesis is needed for posttranscriptional regulation of DNMT1 mRNA, which suggests the involvement of an RNase and/or mRNA stabilization protein entity in DNMT1 transcript stabilization. Our findings suggest that TSA not only alters histone acetylation, but also may affect DNA methylation.
Januchowski
Radosław
R
Department of Biochemistry and Molecular Biology, Karol Marcinkowski University of Medical Sciences, 60-781 Poznań, Poland.
Dabrowski
Mikołaj
M
Ofori
Harold
H
Jagodzinski
Paweł P
PP
D000704:Analysis of Variance; D015153:Blotting, Western; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D019169:Jurkat Cells; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human