研究通过全基因组分析比较了正常结肠黏膜和结直肠癌（CRC）肿瘤中组蛋白修饰H3K4me3和H3K27me3的模式，发现改变具有重要功能后果的修饰较为罕见。尽管H3K4me3在正常组织和细胞系中表现出相似性，但H3K27me3的差异揭示细胞系可能不适合作为组织模型。此外，分析还发现了CRC中表达模式的新变化，H3K4me3阳性基因在肿瘤中过度激活，而H3K27me3阳性基因则过度沉默。这些结果强调了组蛋白修饰在癌症发生中的表观遗传贡献，并可能指示新的生物标志物。
摘要：
Background Despite their well-established functional roles, histone modifications have received less attention than DNA methylation in the cancer field. In order to evaluate their importance in colorectal cancer (CRC), we generated the first genome-wide histone modification profiles in paired normal colon mucosa and tumor samples. Methods Chromatin immunoprecipitation and microarray hybridization (ChIP-chip) was used to identify promoters enriched for histone H3 trimethylated on lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in paired normal colon mucosa and tumor samples from two CRC patients and for the CRC cell line HT29. Results By comparing histone modification patterns in normal mucosa and tumors, we found that alterations predicted to have major functional consequences were quite rare. Furthermore, when normal or tumor tissue samples were compared to HT29, high similarities were observed for H3K4me3. However, the differences found for H3K27me3, which is important in determining cellular identity, indicates that cell lines do not represent optimal tissue models. Finally, using public expression data, we uncovered previously unknown changes in CRC expression patterns. Genes positive for H3K4me3 in normal and/or tumor samples, which are typically already active in normal mucosa, became hyperactivated in tumors, while genes with H3K27me3 in normal and/or tumor samples and which are expressed at low levels in normal mucosa, became hypersilenced in tumors. Conclusions Genome wide histone modification profiles can be used to find epigenetic aberrations in genes associated with cancer. This strategy gives further insights into the epigenetic contribution to the oncogenic process and may identify new biomarkers.
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