Correlation between histone acetylation and expression of the MYO18B gene in human lung cancer cells
- 26 March 2004
- journal article
- research article
- Published by Wiley in Genes, Chromosomes and Cancer
- Vol. 40 (2), 146-151
- https://doi.org/10.1002/gcc.20027
Abstract
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.Keywords
This publication has 19 references indexed in Scilit:
- Critical Role of Histone Methylation in Tumor Suppressor Gene Silencing in Colorectal CancerMolecular and Cellular Biology, 2003
- Heterogeneity in the modification and involvement of chromatin components of the CpG island of the silenced human CDH1 gene in cancer cellsNucleic Acids Research, 2002
- The fundamental role of epigenetic events in cancerNature Reviews Genetics, 2002
- Inactivation of p57KIP2 by regional promoter hypermethylation and histone deacetylation in human tumorsOncogene, 2002
- Histone acetylation: a switch between repressive and permissive chromatinEMBO Reports, 2002
- Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA componentNature Genetics, 2002
- Altered chromatin structure associated with methylation-induced gene silencing in cancer cells: correlation of accessibility, methylation, MeCP2 binding and acetylationNucleic Acids Research, 2001
- Selective association of the methyl-CpG binding protein MBD2 with the silent p14/p16 locus in human neoplasiaProceedings of the National Academy of Sciences of the United States of America, 2001
- Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancerNature Genetics, 1999
- Crystal structure of the nucleosome core particle at 2.8 Å resolutionNature, 1997