Role of histone modifications and DNA methylation in the regulation of O6-methylguanine-DNA methyltransferase gene expression in human stomach cancer cells.
To determine a possible function of histone modifications in stomach carcinogenesis, we analyzed global and MGMT-promoter levels of di-methyl-H3-K9, di-methyl-H3-K4 and acetyl-H3-K9, as well as MGMT DNA methylation and mRNA expression following treatment with 5-aza-2' -deoxycytidine and/or Trichostatin A. We found that histone H3-K9 di-methylation, H3-K4 di-methylation, H3-K9 acetylation and DNA methylation work in combination to silence MGMT. The results indicate that histone modifications as well as DNA methylation may be involved in stomach carcinogenesis. In addition to its effect on DNA methylation, 5-aza-2' -deoxycytidine can act at histone modification level to reactivate MGMT expression in a region-specific and DNA methylation-dependent manner.
Department of Surgical Oncology, the First Affiliated Hospital, China Medical University, Shenyang, China.
Chun-Feng
CF
Meng
Xin-Jiang
XJ
Zhu
Guo
G
Peng
Dong-Qiu
DQ
Dai
D000107:Acetylation; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000209:etiology / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D006657:Histones; D006877:Hydroxamic Acids; D025521:Tumor Suppressor Proteins; C012589:trichostatin A; D000077209:Decitabine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D001374:Azacitidine