The hepatocyte nuclear factor HNF1A is a potential regulator in shaping the super-enhancer landscape in colorectal cancer liver metastasis.

Super-enhancers (SEs) play essential roles in colorectal cancer (CRC) progression. However, how the SE landscape is orchestrated by transcriptional regulators and evolves is not clear. Using de novo motif analysis, we show that the hepatocyte nuclear factor 1 (HNF1)-binding motif is enriched in SEs in cell lines derived from liver metastases, but not in those from primary tumors. This finding was further validated by extending the method to pancreatic cancer and a pair of isogenic CRC lines. Next, we revealed HNF1A was majorly expressed and upregulated in CRC liver metastatic cell lines. Clinically, HNF1A was remarkably upregulated in synchronous liver metastases as compared to localized tumors. Collectively, our study implicates HNF1A as a key regulator in shaping the SE landscape in CRC liver metastasis.