Project description:DNA methylation is an epigenetic mark that is altered in cancer and aging tissues. The effects of extrinsic factors on DNA methylation remain incompletely understood. Microbial dysbiosis is a hallmark of colorectal cancer, and infections have been linked to aberrant DNA methylation in cancers of the GI tract. To determine the microbiota’s impact on DNA methylation, we studied the DNA methylation of colorectal mucosa in germ-free (GF, no microbiome) and specific pathogen free (SPF, controlled microbiome) mice, as well as in interleukin 10 KO mice (Il10-/-) which are prone to inflammation and tumorigenesis in the presence of a microbiome. We compared DNA methylation changes to those seen in aging, and after exposure to the colon carcinogen azoxymethane (AOM). DNA methylation changes associated with aging were accelerated in the Il10-/- /SPF mice. By contrast, AOM induced profound hypomethylation that was distinct from the effects of aging or of the microbiome. CpG sites modified by the microbiome were over-represented among DNA methylation changes in colorectal cancer. Thus, the microbiome affects the DNA methylome of colorectal mucosa in patterns reminiscent of what is observed in colorectal cancer.
Project description:Gene expression in the colonic mucosa of wild-type and p38a-knockout intestinal epithelial cells (IECs) were compared. C57BL/6 wild-type mice, and intestinal epithelial cell-specific p38a-knockout mice on a C57BL/6 background were used for isolation of colonic mucosa
Project description:To investigate whether lifestyle factors modulate the stability of gene promoter methylation in the normal aging colonic mucosa, we performed genome-scale DNA methylation profiling of 178 normal colon biopsies using the Illumina Infinium DNA methylation assay, which assesses the DNA methylation status of 27,578 CpG sites located at the promoter regions of 14,495 protein-coding genes. We identified Aspirin use and hormonal replacement therapy (HRT) suppress, whereas a high body mass index (BMI) and smoking promote age-related hyermethylation. Many of these loci modulated by lifestyle in the healthy colon mucosa coincide with loci hypermethylated in colorectal cancers and down-regulated in adenomas. The data show that lifestyle modulates the stability of DNA methylation in the aging colonic epithelium and thereby impacts the rate of evolution of cancer methylomes. Bisulphite converted DNA from the 178 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
Project description:Gene expression in the colonic mucosa of wild-type and p38a-knockout intestinal epithelial cells (IECs) were compared. C57BL/6 wild-type mice, and intestinal epithelial cell-specific p38a-knockout mice on a C57BL/6 background were used for isolation of colonic mucosa Gene expression in each genotype was analyzed in triplicate.
Project description:To investigate whether lifestyle factors modulate the stability of gene promoter methylation in the normal aging colonic mucosa, we performed genome-scale DNA methylation profiling of 178 normal colon biopsies using the Illumina Infinium DNA methylation assay, which assesses the DNA methylation status of 27,578 CpG sites located at the promoter regions of 14,495 protein-coding genes. We identified Aspirin use and hormonal replacement therapy (HRT) suppress, whereas a high body mass index (BMI) and smoking promote age-related hyermethylation. Many of these loci modulated by lifestyle in the healthy colon mucosa coincide with loci hypermethylated in colorectal cancers and down-regulated in adenomas. The data show that lifestyle modulates the stability of DNA methylation in the aging colonic epithelium and thereby impacts the rate of evolution of cancer methylomes.
Project description:ATAC-seq on human colonic mucosa For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:w61 colonic mucosa For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:These samples have been analyzed for global alternative splicing variation on exon-level expression data using the FIRMA algorithm. We have identified and described transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of solid cancers. This Series consists of 19 normal colonic mucosa samples from colorectal cancer patients, and is an amendment to a larger series of colorectal cancer and adjacent normal colonic mucosa samples analyzed for gene expression at the exon-level (GSE24550).
Project description:Control ChIP-seq on colonic mucosa tissue female adult (41 years) For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
Project description:H3K27ac ChIP-seq on colonic mucosa tissue female adult (41 years) For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf