Loss of epigenetic suppression of retrotransposons with oncogenic potential in aging mammary luminal epithelial cells [RESEARCH]

We report here that several TE subfamilies function as regulatory elements in normal LEps, and a subset of these display consistent methylation changes with age. Methylation changes at these TEs occurred at lineage-specific transcription factor binding sites, consistent with loss of lineage specificity. Whereas TEs mainly showed methylation loss, CpG islands (CGIs) that are targets of the Polycomb repressive complex 2 (PRC2) show a gain of methylation in aging cells. Many TEs with methylation loss in aging LEps have evidence of regulatory activity in breast cancer samples. We furthermore show that methylation changes at TEs impact the regulation of genes associated with luminal breast cancers. These results indicate that aging leads to DNA methylation changes at TEs that undermine the maintenance of lineage specificity, potentially increasing susceptibility to breast cancer.

Source: Genome Research - September 11, 2023 Category: Genetics & Stem Cells Authors: Senapati, P., Miyano, M., Sayaman, R. W., Basam, M., Leung, A., LaBarge, M. A., Schones, D. E. Tags: RESEARCH Source Type: research