DNA methylation critically influences colorectal cancer (CRC) development and metastasis, yet the precise effects at individual genomic sites are not fully elucidated. Previously, we found that hypomethylation at cg24067911 correlates with poor outcomes in CRC patients. To clarify the role of cg24067911 in metastatic progression, we used the CRISPR-dCas9-DNMT3a system to selectively modify its methylation. Integrating transposase-accessible chromatin sequencing, RNA sequencing, and chromatin immunoprecipitation revealed that cg24067911 lies within an ATXN1 enhancer and serves as a binding site for BCL6. Reduced methylation at this locus strengthened BCL6 interaction, boosting ATXN1 expression. In turn, ATXN1 functions as a transcriptional regulator of CDH2, driving epithelial-mesenchymal transition and enhancing metastatic potential in CRC. These findings uncover a novel epigenetic pathway—the BCL6–ATXN1–CDH2 axis—through which cg24067911 methylation impacts metastasis, highlight its prognostic value, and propose targeted epigenetic editing as a potential therapeutic approach to limit CRC spread.
