Genome-wide H3K9 histone acetylation profiles are altered in benzopyrene-treated MCF7 breast cancer cells.
Current toxicogenomic approaches generate transcriptional profiles that can identify functional gene expression signatures of environmental toxicants. However, the intricate processes governing transcription are overlaid with a complex set of molecular instructions involving epigenetic modifications. These commands regulate both gene expression and chromatin organization through coordinated sets of histone modifications and heritable DNA methylation patterns. Although the effects of specific environmental toxicants on gene expression are the subject of much study, the epigenetic effects of such compounds are poorly understood. Here we have used human promoter tiling arrays along with chromatin immunoprecipitation to identify changes in histone acetylation profiles because of chemical exposure. Chromatin from cells exposed to the polyaromatic hydrocarbon benzo(a)pyrene was immunoprecipitated with antibodies against acetylated histones. Affymetrix promoter tiling microarrays were probed to generate epigenomic profiles of hypo- and hyperacetylated chromatin localized to gene promoter regions. Statistical analyses, data mining, and expression studies revealed that treated cells possessed differentially acetylated gene promoter regions and gene-specific expression changes. This chromatin immunoprecipitation-on-chip approach permits genome-wide profiling of histone acetylation patterns that can identify chromatin-related signatures of environmental toxicants and potentially determine the molecular pathways these changes target. This approach also has potential applications for profiling histone modifications and DNA methylation changes during embryonic development, in cancer biology, and in the development and assessment of cancer therapeutics.
Sadikovic
Bekim
B
London Regional Cancer Program, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada.
Andrews
Joseph
J
Carter
David
D
Robinson
John
J
Rodenhiser
David I
DI
D000107:Acetylation; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism*; D006801:Humans; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
D006657:Histones; D001564:Benzo(a)pyrene