Correlation between histone acetylation and expression of the MYO18B gene in human lung cancer cells.
Recently, we isolated a candidate tumor-suppressor gene, MYO18B, which was inactivated in approximately 50% of human lung cancers by deletion, mutation, and promoter methylation. However, more frequent reduction or loss of MYO18B expression and restoration of MYO18B expression by trichostatin A (TSA) treatment suggested the contribution of other mechanisms, especially histone deacetylation, for epigenetic inactivation of the MYO18B gene. In this study, we examined histone modification of the promoter region of the MYO18B gene in 8 human lung cancer cell lines by a chromatin immunoprecipitation assay. In 6 of 7 cell lines with reduced or silenced MYO18B expression, the levels of histones H3 and H4 acetylation surrounding the MYO18B promoter region were lower than those in a cell line with MYO18B expression. By treatment with TSA, the levels of histone H3 and H4 acetylation were increased in all 6 cell lines whose MYO18B expression was restored by TSA, whereas neither H3 nor H4 acetylation was increased in cells whose MYO18B expression was not restored by TSA. Significant correlations were observed between the levels of histone H3/H4 acetylation and MYO18B expression. These results suggest that acetylation of both histones H3 and H4 contributes to regulation of MYO18B expression in lung cancer cells and that histone deacetylation surrounding the promoter region plays an important role in MYO18B silencing and is involved in lung carcinogenesis.
Tani
Masachika
M
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Ito
Jun
J
Nishioka
Michiho
M
Kohno
Takashi
T
Tachibana
Ken
K
Shiraishi
Masahiko
M
Takenoshita
Seiichi
S
Yokota
Jun
J
D000107:Acetylation / Q000187:drug effects; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology
D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D018995:Myosin Heavy Chains