Histone H4 deacetylation down-regulates catalase gene expression in doxorubicin-resistant AML subline

• Published in: Cell biology and toxicology 2012-02, Vol.28 (1), p.11-18
• Main Authors: Lee, Tae-Bum, Moon, Young-Sook, Choi, Cheol-Hee
• Format: Article
• Language: English
• Subjects: 5-aza-2'-deoxycytidine; Acetylation; Acetylation - drug effects; Acute myeloid leukemia; Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Biochemistry; Biomedical and Life Sciences; Catalase; Catalase - drug effects; Catalase - genetics; Catalase - metabolism; Cell Biology; Cell Line, Tumor; Cellular biology; Chromatin; CpG islands; Deacetylation; DNA methylation; DNA Modification Methylases - antagonists & inhibitors; Down-Regulation - drug effects; Doxorubicin - pharmacology; Drug Resistance - genetics; Enzymes; Epigenetics; Gene expression; Histone deacetylase; Histone Deacetylase Inhibitors - pharmacology; Histone H4; Histones - drug effects; Histones - metabolism; Humans; Hydrogen peroxide; Hydroxamic Acids - administration & dosage; Immunoprecipitation; Leukemia; Life Sciences; Original Research; Oxidative stress; Peroxidase; Pharmacology/Toxicology; Polymerase chain reaction; Protein Modification, Translational; Trichostatin A
• ISSN: 0742-2091; 1573-6822
• DOI: 10.1007/s10565-011-9201-y

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.