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

Tomomitsu Doi; Hironori Hojo; Shinsuke Ohba; Kunie Obayashi; Motoyoshi Endo; Toshimasa Ishizaki; Akira Katoh; Hiroyuki Kouji

doi:10.1016/j.heliyon.2022.e08890

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

Heliyon. 2022 Feb 2;8(2):e08890. doi: 10.1016/j.heliyon.2022.e08890. eCollection 2022 Feb.

Authors

Tomomitsu Doi^{1

2

3}, Hironori Hojo², Shinsuke Ohba^{2

4}, Kunie Obayashi¹, Motoyoshi Endo¹, Toshimasa Ishizaki³, Akira Katoh⁵, Hiroyuki Kouji^{6

7}

Affiliations

¹ Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
² Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8656, Japan.
³ Department of Pharmacology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan.
⁴ Department of Cell Biology, Institute of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8588, Japan.
⁵ Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan.
⁶ Translational Chemical Biology Laboratory, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama, Yufu, Oita, 879-5593, Japan.
⁷ Oita University Institute of Advanced Medicine, Inc., 17-20, Higashi Kasuga-machi, Oita-city, Oita, 870-0037, Japan.

Abstract

Wnt/β-catenin is believed to regulate different sets of genes with different coactivators, cAMP response element-binding 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.

Keywords: AP-1; Coactivator CREB-binding protein; Wnt; p300; β-catenin.