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  • The EMBO Journal (2007) 26, 764 - 774
  • doi:10.1038/sj.emboj.7601548

Published online: 25 January 2007

A cell cycle-dependent co-repressor mediates photoreceptor cell-specific nuclear receptor function

Shinichiro Takezawa1,4, Atsushi Yokoyama1, Maiko Okada1, Ryoji Fujiki1, Aya Iriyama2, Yasuo Yanagi2, Hiroaki Ito1, Ichiro Takada1, Masahiko Kishimoto1, Atsushi Miyajima1, Ken-ichi Takeyama1, Kazuhiko Umesono3, Hirochika Kitagawa1 and Shigeaki Kato1,4

  1. The Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan
  2. Department of Ophthalmology, University of Tokyo, School of Medicine, Bunkyo-ku, Tokyo, Japan
  3. Institute for Virus Research, and Graduate School for Biostudies, Kyoto University, Kyoto, Japan
  4. ERATO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan

Correspondence to:

Shigeaki Kato, Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. Tel.: +81 3 5841 8478; Fax: +81 3 5841 8477; E-mail: uskato@mail.ecc.u-tokyo.ac.jp

Received 9 November 2006; Accepted 15 December 2006

Photoreceptor cell-specific nuclear receptor (PNR) (NR2E3) acts as a sequence-specific repressor that controls neuronal differentiation in the developing retina. We identified a novel PNR co-repressor, Ret-CoR, that is expressed in the developing retina and brain. Biochemical purification of Ret-CoR identified a multiprotein complex that included E2F/Myb-associated proteins, histone deacetylases (HDACs) and NCoR/HDAC complex-related components. Ret-CoR appeared to function as a platform protein for the complex, and interacted with PNR via two CoRNR motifs. Purified Ret-CoR complex exhibited HDAC activity, co-repressed PNR transrepression function in vitro, and co-repressed PNR function in PNR target gene promoters, presumably in the retinal progenitor cells. Notably, the appearance of Ret-CoR protein was cell-cycle-stage-dependent (from G1 to S). Therefore, Ret-CoR appears to act as a component of an HDAC co-repressor complex that supports PNR repression function in the developing retina, and may represent a co-regulator class that supports transcriptional regulator function via cell-cycle-dependent expression.

  • Keywords:

    • cell cycle,
    • co-repressor complex,
    • HDAC,
    • PNR,
    • retina