GSE161558
Super-enhancer landscape shaped by master regulator in liver metastasis of colorectal cancer [ChIP-seq]
We interrogated global super-enhancer landscape and sought to discover master regulators governing the liver metastasis of colorectal cancer (CRC). Using de novo analysis, we predicted motif enrichment of master transcription factor in super-enhancers. We show that transcription factor-binding sites of hepatocyte nuclear factor 1 (HNF1) family are enriched at super-enhancers identified in cell lines derived from liver metastases, but not those derived from primary tumors. Using ChIP-Seq of acetylated H3K27, the enrichment of HNF1 binding motifs in super enhancers was found in a cell line derived from xenografted liver metastasis but not the parental cell line. The prediction method was further extended to pancreatic cancer where liver metastasis is also a common finding, and a similar enrichment of HNF1 family motif in super-enhancers was found. We subsequently showed that HNF1A was prominently expressed and significantly upregulated in metastatic cell lines and clinical specimens of liver metastases. Collectively, our study implicates HNF1A as a master transcription factor involved in shaping global super-enhancer landscape in CRC liver metastasis. Overall design: Examination of H3K27ac profile in KM12SM and parental KM12C cells