Transcriptional Coactivator PC4 Stimulates Promoter Escape and Facilitates Transcriptional Synergy by GAL4-VP16

  • Aya Fukuda
    Department of Molecular Biology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan
  • Tomoyoshi Nakadai
    Department of Molecular Biology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan
  • Miho Shimada
    Department of Molecular Biology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan
  • Tohru Tsukui
    Department of Molecular Biology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan
  • Masahito Matsumoto
    Department of Molecular Biology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan
  • Yasuhisa Nogi
    Department of Molecular Biology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan
  • Michael Meisterernst
    Gene Expression, Institute of Molecular Immunology, GSF-National Research Center for Environment and Health, Munich, Germany
  • Koji Hisatake
    Department of Molecular Biology, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan

書誌事項

公開日
2004-07-01
権利情報
  • https://journals.asm.org/non-commercial-tdm-license
DOI
  • 10.1128/mcb.24.14.6525-6535.2004
公開者
Informa UK Limited

説明

Positive cofactor 4 (PC4) is a coactivator that strongly augments transcription by various activators, presumably by facilitating the assembly of the preinitiation complex (PIC). However, our previous observation of stimulation of promoter escape in GAL4-VP16-dependent transcription in the presence of PC4 suggested a possible role for PC4 in this step. Here, we performed quantitative analyses of the stimulatory effects of PC4 on initiation, promoter escape, and elongation in GAL4-VP16-dependent transcription and found that PC4 possesses the ability to stimulate promoter escape in response to GAL4-VP16 in addition to its previously demonstrated effect on PIC assembly. This stimulatory effect of PC4 on promoter escape required TFIIA and the TATA box binding protein-associated factor subunits of TFIID. Furthermore, PC4 displayed physical interactions with both TFIIH and GAL4-VP16 through its coactivator domain, and these interactions were regulated distinctly by PC4 phosphorylation. Finally, GAL4-VP16 and PC4 stimulated both initiation and promoter escape to similar extents on the promoters with three and five GAL4 sites; however, they stimulated promoter escape preferentially on the promoter with a single GAL4 site. These results provide insight into the mechanism by which PC4 permits multiply bound GAL4-VP16 to attain synergy to achieve robust transcriptional activation.

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