Involvement of activator protein-1 family members in β-catenin and p300 association on the genome of PANC-1 cells

Abstract

Wnt/β-catenin is believed to regulate different sets of genes with different coactivators, cAMP response elementbinding protein (CREB)-binding protein (CBP) or p300. However, the factors that determine which coactivators act on a particular promoter remain elusive. ICG-001 is a specific inhibitor for β-catenin/CBP but not for β-catenin/p300. By taking advantage of the action of ICG-001, we sought to investigate regulatory mechanisms underlying β-catenin coactivator usage in human pancreatic carcinoma PANC-1 cells through combinatorial analysis of chromatin immunoprecipitation-sequencing and RNA-sequencing. CBP and p300 preferentially bound to regions with the TCF motif alone and with both the TCF and AP-1 motifs, respectively. ICG-001 increased β-catenin binding to regions with both the TCF and AP-1 motifs, flanking the genes induced by ICG-001, concomitant with the increments of the p300 and AP-1 component c-JUN binding. Taken together, AP-1 possibly coordinates β-catenin coactivator usage in PANC-1 cells. These results would further our understanding of the canonical Wnt/ β-catenin signaling divergence.

ANGPTL8 links inflammation and poor differentiation, which are characteristics of malignant renal cell carcinoma

“…Real‐time quantitative RT‐PCR was carried out as described. 29 Oligonucleotide primers are listed in Tables S1 .…”