A cell cycle-dependent co-repressor mediates photoreceptor cell-specific nuclear receptor function.
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.
Takezawa
Shinichiro
S
The Institute of Molecular and Cellular Biosciences, University of Tokyo, Yayoi, Bunkyo-ku, Tokyo, Japan.
Yokoyama
Atsushi
A
Okada
Maiko
M
Fujiki
Ryoji
R
Iriyama
Aya
A
Yanagi
Yasuo
Y
Ito
Hiroaki
H
Takada
Ichiro
I
Kishimoto
Masahiko
M
Miyajima
Atsushi
A
Takeyama
Ken-Ichi
K
Umesono
Kazuhiko
K
Kitagawa
Hirochika
H
Kato
Shigeaki
S
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*
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