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Exercise-associated epigenetic remodeling and TCR repertoire dynamicsin Lynch Syndrome carriers (RRBS)

ABSTRACT: Lynch Syndrome (LS) carriers are at elevated cancer risk. Recent data suggest exercise as a non-pharmacologic preventive strategy, yet the epigenetic and immunological mechanisms underlying its protective effects in this population remain unclear. Here, we perform integrative multi-omics profiling of DNA methylation, gene expression, and the T cell receptor (TCR) repertoire in LS carriers participating in a 52-week aerobic cycling intervention. We identify compartment-specific DNA methylation changes, including innate immune activation in cfDNA and oncogenic pathway repression in tissue. Transcriptomic integration highlights ISL1 as a key exercise-repressed gene and FLCN as a CRC-associated methylation target. TCR analysis reveals increased systemic repertoire diversity and tissue-specific clonal convergence, thus suggesting antigen-driven recruitment. These findings uncover epigenetic and immune remodeling as potential mechanisms of exercise-mediated protection in LS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE309783 | GEO | 2026/08/03

REPOSITORIES: GEO

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Exercise-associated epigenetic remodeling and TCR repertoire dynamicsin Lynch Syndrome carriers (MEDIP-seq)

Project description:Lynch Syndrome (LS) carriers are at elevated cancer risk. Recent data suggest exercise as a non-pharmacologic preventive strategy, yet the epigenetic and immunological mechanisms underlying its protective effects in this population remain unclear. Here, we perform integrative multi-omics profiling of DNA methylation, gene expression, and the T cell receptor (TCR) repertoire in LS carriers participating in a 52-week aerobic cycling intervention. We identify compartment-specific DNA methylation changes, including innate immune activation in cfDNA and oncogenic pathway repression in tissue. Transcriptomic integration highlights ISL1 as a key exercise-repressed gene and FLCN as a CRC-associated methylation target. TCR analysis reveals increased systemic repertoire diversity and tissue-specific clonal convergence, thus suggesting antigen-driven recruitment. These findings uncover epigenetic and immune remodeling as potential mechanisms of exercise-mediated protection in LS.

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Exercise-associated epigenetic remodeling and TCR repertoire dynamicsin Lynch Syndrome carriers (RRBS)

Project description:Exercise-associated epigenetic remodeling and TCR repertoire dynamicsin Lynch Syndrome carriers (RRBS)

| PRJNA1363163 | ENA

Exercise-associated epigenetic remodeling and TCR repertoire dynamicsin Lynch Syndrome carriers (MEDIP-seq)

Project description:Exercise-associated epigenetic remodeling and TCR repertoire dynamicsin Lynch Syndrome carriers (MEDIP-seq)

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