title: Cell density-dependent nuclear accumulation of ELK3 is involved in suppression of PAI-1 expression.
abstract: Cell-cell contact regulates the proliferation and differentiation of non-transformed cells, e.g., NIH/3T3 cells show growth arrest at high cell density. However, only a few reports described the dynamic behavior of transcription factors involved in this process. In this study, we showed that the mRNA levels of plasminogen activator inhibitor type 1 (PAI-1) decreased drastically at high cell density, and that ELK3, a member of the Ets transcription factor family, repressed PAI-1 expression. We also demonstrated that while ELK3 was distributed evenly throughout the cell at low cell density, it accumulated in the nucleus at high cell density, and that binding of DNA by ELK3 at the A domain facilitated its nuclear accumulation. Furthermore, we found that ETS1, a PAI-1 activator, occupied the ELK3-binding site within the PAI-1 promoter at low cell density, while it was released at high cell density. These results suggest that at high cell density, the switching of binding of transcription factors from ETS1 to ELK3 occurs at a specific binding site of the PAI-1 promoter, leading to the cell-density dependent suppression of PAI-1 expression.
authors.affiliation: Department of Frontier Biosciences, Graduate School of Frontier Biosciences, Osaka University, Yamada-oka, Suita, Osaka, Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Tanaka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakao
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sekimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Oka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002452:Cell Count; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D016153:Genes, Suppressor; D051379:Mice; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058258:Serpin E2 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C086924:Elk3 protein, mouse; C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D058258:Serpin E2; C511869:Serpine2 protein, mouse