The ZMYND8-regulated Mevalonate Pathway Endows YAP-High Intestinal Cancer with Metabolic Vulnerability

To elucidate the molecular basis by which ZMYND8 influences intestinal stemness and tumorigenesis, we performed RNA-seq to analyze gene expression in the crypts of 2-month-old Apcmin/+ and Apcmin/+; Zmynd8IEC–/– mice. Next, we performed chromatin immunoprecipitation (ChIP) sequencing (ChIP-Seq) to characterize the genomic distribution of ZMYND8 and SREBP2 in HCT116 WT and SREBP2-KO cells under sterol-depleted conditions. Total RNA was extracted from small intestinal crypts of 2-month-old Apcmin/+ and ZMYND8IEC-/-; Apcmin/+ mice. Each RNA sample contained 3 mice replicates and was pooled by equal mass to diminish variation. For ChIP sequencing, HCT116 WT and SREBP2-KO cells were cultured in LPDS for 24 hours and crosslinked. The pellets were harvested and performed by ChIP seq using ZMYND8 antibody (Bethyl A302-090A) and SREBP2 antibody (Cayman, 10007663).