scholarly journals The Corepressor CTBP2 Is a Coactivator of Retinoic Acid Receptor/Retinoid X Receptor in Retinoic Acid Signaling

2013 ◽  
Vol 33 (16) ◽  
pp. 3343-3353 ◽  
Author(s):  
Prashanth Kumar Bajpe ◽  
Guus J. J. E. Heynen ◽  
Lorenza Mittempergher ◽  
Wipawadee Grernrum ◽  
Iris A. de Rink ◽  
...  

Retinoids play key roles in development, differentiation, and homeostasis through regulation of specific target genes by the retinoic acid receptor/retinoid X receptor (RAR/RXR) nuclear receptor complex. Corepressors and coactivators contribute to its transcriptional control by creating the appropriate chromatin environment, but the precise composition of these nuclear receptor complexes remains to be elucidated. Using an RNA interference-based genetic screen in mouse F9 cells, we identified the transcriptional corepressor CTBP2 (C-terminal binding protein 2) as a coactivator critically required for retinoic acid (RA)-induced transcription.CTBP2suppression by RNA interference confers resistance to RA-induced differentiation in diverse murine and human cells. Mechanistically, we find that CTBP2 associates with RAR/RXR at RA target gene promoters and is essential for their transactivation in response to RA. We show that CTBP2 is indispensable to create a chromatin environment conducive for RAR/RXR-mediated transcription by recruiting the histone acetyltransferase p300. Our data reveal an unexpected function of the corepressor CTBP2 as a coactivator for RAR/RXR in RA signaling.

1998 ◽  
Vol 136 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Masato Ikeda ◽  
Remco A Spanjaard ◽  
Elizabeth W Noordhoek ◽  
Akio Kawaguchi ◽  
Toshimasa Onaya ◽  
...  

2014 ◽  
Vol 42 (2) ◽  
pp. 587-605 ◽  
Author(s):  
Kohichi Kawahara ◽  
Michita Suenobu ◽  
Hideyuki Ohtsuka ◽  
Akihiko Kuniyasu ◽  
Yukihiko Sugimoto ◽  
...  

Oncogene ◽  
2003 ◽  
Vol 22 (57) ◽  
pp. 9142-9150 ◽  
Author(s):  
Frédéric Pendino ◽  
Charles Dudognon ◽  
Francois Delhommeau ◽  
Tewfik Sahraoui ◽  
Maria Flexor ◽  
...  

1992 ◽  
Vol 12 (12) ◽  
pp. 5527-5535 ◽  
Author(s):  
R K Hall ◽  
D K Scott ◽  
E L Noisin ◽  
P C Lucas ◽  
D K Granner

The accessory factor 1 (AF1) element is an upstream transcriptional control region that plays a role in the response of the phosphoenolpyruvate carboxykinase (PEPCK) gene to both glucocorticoids and retinoic acid. We demonstrate here that retinoic acid receptor alpha (RAR alpha) binds to a sequence within the AF1 element, TGACCT (site B), that is a consensus retinoic acid response element (RARE) half-site. A similar DNA sequence, TGGCCG (site C), located 1 bp downstream of site B, is not involved in the binding of RAR alpha monomers or dimers but is required for the constitution of a functional RARE. Site C is also required for the formation of a complex involving RAR alpha and a liver nuclear factor designated CR, for coregulator. Mutational analysis of the AF1 element shows that the RAR alpha/CR complex is the trans-acting unit that mediates the retinoic acid response of the PEPCK gene. Another member of the retinoid receptor family, retinoid X receptor alpha (RXR alpha), can also form a complex with RAR alpha and the AF1 element. Several observations, including the observation that RXR alpha antibody interacts with CR, indicate that RXR alpha and CR are identical or closely related proteins. Through RXR alpha forms a complex with RAR alpha and the AF1 element, we demonstrate that the AF1 element is functionally distinguishable from a retinoid X response element. Taken together, our results show that the AF1 element contains an RARE that mediates a retinoic acid response by binding an RAR alpha/coregulator complex; this coregulator is presumably RXR alpha.


1998 ◽  
Vol 17 (5) ◽  
pp. 462-469 ◽  
Author(s):  
Nicole M. Bossenbroek ◽  
Timothy H. Sulahian ◽  
John L. Ubels

2001 ◽  
Vol 85 (1) ◽  
pp. 60-69 ◽  
Author(s):  
Takayuki Hida ◽  
Kenji Tai ◽  
Naoki Tokuhara ◽  
Akira Ishibashi ◽  
Kouichi Kikuchi ◽  
...  

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