Assessment of Histone Tail Modifications and Transcriptional Profiling During Colon Cancer and Role of fish oil/pectin Diet Against Colon Carcinogen

In an effort to gain insight into the extensive dimension of post-translational modifications in histones (including H3K4me3 and H3K9ac) and elucidate the chemoprotective impact of dietary bioactive compounds on transcriptional control in a colon cancer preclinical model, we generated high-resolution genome-wide RNA (RNA-Seq) and “chromatin-state” (H3K4me3-seq and H3K9ac-seq) maps for intestinal (epithelial colonocytes) crypts in rats treated with a colon carcinogen and fed bioactive (i) fish oil (ii) butyrate (in the form of a fermentable fiber a rich source of SCFA), (iii) a combination of fish oil plus butyrate or (iv) control diets. Poor correlation was observed between differentially transcribed (DE) and enriched genes (DERs) at multiple epigenetic levels in fat x fiber dietary combinations and in the presence/absence of carcinogen. We also demonstrated that the combinatorial diet (fish oil + pectin) was synergistically chemoprotective, and uniquely affected epigenetic profiles in the intestinal epithelium, e.g., upregulating lipid catabolism and beta-oxidation associated genes. Examination of 2 different histone modifications in rat colonocytes in a 2x2x2 factorial study cancer x oil x fiber