title: A cell cycle-dependent co-repressor mediates photoreceptor cell-specific nuclear receptor function.
abstract: 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.
authors.affiliation: The Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takezawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Maiko
authors.initials: M
authors.lastname: Okada
authors.forename: Ryoji
authors.initials: R
authors.lastname: Fujiki
authors.forename: Aya
authors.initials: A
authors.lastname: Iriyama
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yanagi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ito
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takada
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takeyama
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Umesono
authors.forename: Hirochika
authors.initials: H
authors.lastname: Kitagawa
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D006655:Histone Deacetylases / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D057093:Orphan Nuclear Receptors; D010786:Photoreceptor Cells / Q000196:embryology*; D020365:RNA Helicases; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; C485736:Nr2e3 protein, mouse; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D006655:Histone Deacetylases; D020365:RNA Helicases; C518156:Ret-CoR protein, mouse