title: Histone H4 deacetylation down-regulates catalase gene expression in doxorubicin-resistant AML subline.
abstract: We explored if epigenetic mechanisms could be involved in the down-regulated expression of catalase gene (CAT) in the doxorubicin-resistant acute myelogenous leukemia (AML)-2/DX100 cells. Down-regulated CAT expression in AML-2/DX100 cells was completely recovered after treatment of hydrogen peroxide (H(2)O(2)) and histone deacetylase inhibitor, trichostatin A (TSA) but was increased slightly by the treatment of DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-AdC). Bisulfite-sequencing PCR revealed that a CpG island of CAT was not methylated in AML-2/DX100 cells. Chromatin immunoprecipitation assay confirmed that acetylation of histone H4 in AML-2/DX100 cells significantly decreased as compared with that in AML-2/WT cells, which was significantly increased by TSA more than 5-AdC. Meanwhile, overexpression of other up-regulated peroxidase genes appears to make compensation for decreased H(2)O(2)-scavenging activity for the down-regulated CAT expression in AML-2/DX100 cells. These results suggest that histone H4 deacetylation is responsible for the down-regulated CAT expression in AML-2/DX100 cells, which are well adapted to oxidative stress.
authors.affiliation: Research Center for Resistant Cells, Chosun University Medical School, Chosun University, Gwangju, 501-759, Republic of Korea.
authors.forename: Tae-Bum
authors.initials: TB
authors.lastname: Lee
authors.forename: Young-Sook
authors.initials: YS
authors.lastname: Moon
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Choi
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006657:Histones / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D046188:Protein Modification, Translational
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D000077209:Decitabine; D004317:Doxorubicin; D002374:Catalase; D015254:DNA Modification Methylases; D001374:Azacitidine