ArticleCancers2026
Cross-Dataset Genomic Proximity and Functional Association of FOXA1 and TET2 at Hypomethylated Regulatory Regions in Colorectal Cancer.
Article in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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11 authors.
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Abstract
BACKGROUND/
objectivesAberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC). However, how pioneer transcription factors are associated with DNA demethylases at cis-regulatory elements and influence tumor-associated transcriptional programs remains poorly understood. This study investigated the functional relationship between FOXA1 and TET2, an enzyme that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and its association with epigenetic features and malignant phenotypes in CRC.
methodsPublic DNA methylation, ChIP-seq, and transcriptomic datasets were integrated with genome-wide genomic-proximity analyses. The association between FOXA1 and TET2 was evaluated by co-immunoprecipitation. FOXA1 and TET2 were individually or simultaneously depleted in HCT116 and SW480 cells, followed by proliferation and invasion assays. In addition, RNA-seq profiles were generated from control, FOXA1-KD, TET2-KD, and Double-KD HCT116 cells to characterize the resulting transcriptional changes.
resultsCRC-associated hypomethylated regions showed preferential enrichment of FOXA1- and TET2-associated ChIP-seq signals. At a 500 bp summit-to-summit threshold, FOXA1-TET2 genomic proximity was 30.7-fold higher than expected under chromosome-wise circular permutation (empirical
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