PRJNA869853
Mus musculus strain:FAH-/- (deltaExon5) Raw sequence reads
Using a multi-omics approach, we integrated high-throughput transcriptome and chromatin profiling of our murine hepatoblastoma model to identify dynamic activity at candidate cis-regulatory elements (cCREs). We observed that 1,301 of 305,596 cCREs exhibit "Tumor-modified" (TM) accessibility in HB. We mapped 241 TM enhancers to corresponding genes using accessibility and H3K27Ac profiles. Anti-YAP1 Cleavage under targets and tagmentation (CUT&amp;Tag) in tumors revealed 66 YAP1-bound TM cCRE/gene pairs, 31 of which decrease expression after YAP1 withdrawal. We validated the YAP1-dependent expression of a putative YAP1 target, Jun Dimerization Protein 2 (JDP2), in human HB cell lines using YAP1 and LATS1/2 siRNA knockdown. We also confirmed YAP1-induced activity of the Jdp2 TM enhancer in vitro, and discovered an analogous human enhancer in silico. Finally, we used transcription factor (TF) footprinting to identify putative YAP1 co-factors and characterize HB-specific TF activity, genome-wide.