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The association of bacteria and host methylation in colorectal cancer

ABSTRACT: The association of bacteria and host methylation in colorectal cancer.

PROVIDER: PRJEB35776 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR3763500.fastq.gz	Fastqsanger.gz
	ERR3763520.fastq.gz	Fastqsanger.gz
	ERR3763530.fastq.gz	Fastqsanger.gz
	ERR3763501.fastq.gz	Fastqsanger.gz
	ERR3763521.fastq.gz	Fastqsanger.gz

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Project description:Aberrant methylation of DNA is supposed to be a major and early driver of colonic adenoma development and may also lead to colorectal cancer (CRC) formation. While gene methylation assays are used already for CRC screening, differential epigenetic alterations of recurring and non-recurring colorectal adenomas have yet not been systematically investigated. Here, we collected a sample set (n=72) of formalin-fixed paraffin-embedded (FFPE) primary colorectal adenomas without recurrence (n=30), primary adenomas with recurrence at the same location (n=19), so-called “matched pair samples” (n=10; comprising the primary adenoma and the recurrent adenoma) and normal mucosa specimens (n=3). We aimed to unveil differentially methylated CpG positions (DMPs) across the methylome of the selected samples using the Illumina HumanMethylation 450K BeadChip array. Unsupervised hierarchical clustering exhibited a significant association of methylation patterns with the histological subtypes. No significant DMPs were identified comparing primary adenomas with and without recurrence. Despite that, a total of 5,094 DMPs (FDR<0.05, fold change>10%) were identified in the comparisons of recurrent adenomas vs. (non-) matched primary adenomas with recurrence (674; 98% hypermethylated), recurrent adenomas vs. primary adenomas with and without recurrence (241; 99% hypermethylated) and adenomas vs. normal mucosae (4,179; 46% hypermethylated). DMPs in CpG islands were frequently hypermethylated whereas open sea and shelves exhibited hypomethylation. Gene ontological analysis demonstrated enrichment of genes associated with the immune system, inflammatory processes, and cancer-pathways. We conclude that methylation data is helpful to contribute to a more stable and reproducible histological adenoma classification which is a prerequisite to establishing profound surveillance guidelines

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Project description:The methylation of ε-amino groups in protein lysine residues is an important posttranslational modification in eukaryotes, influencing various biological processes. In prokaryotes, this modification has been less studied, but recent findings suggest its role in bacterial immune evasion and host cell adhesion. Here, we analyzed Acinetobacter sp. Tol 5 cell surface proteins using LC‒MS, discovering that lysine residues of its trimeric autotransporter adhesin (TAA), AtaA, are specifically methylated. Over 130 of 232 lysine residues in AtaA were methylated. We identified the outer membrane protein lysine methyltransferase (OM PKMT) KmtA, responsible for the methylation. Bioinformatic analysis revealed the wide distribution of OM PKMT genes among gram-negative bacteria, including pathogens with TAAs that promote infection, such as Burkholderia mallei and Haemophilus influenzae. Clustering analysis suggested that KmtA is a new type of OM PKMT. Deletion of Tol 5 KmtA increased AtaA on the cell surface, enhancing adhesion and slowing growth.

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