scholarly journals Differential Effects of Nuclear Receptor Corepressor (N-CoR) Expression Levels on Retinoic Acid Receptor-Mediated Repression Support the Existence of Dynamically Regulated Corepressor Complexes

1997 ◽  
Vol 11 (6) ◽  
pp. 682-692 ◽  
Author(s):  
M. Soderstrom
2000 ◽  
Vol 275 (25) ◽  
pp. 19401-19408 ◽  
Author(s):  
Elliott S. Klein ◽  
Jenny W. Wang ◽  
Berket Khalifa ◽  
Stacey A. Gavigan ◽  
Roshantha A. S. Chandraratna

1995 ◽  
Vol 92 (6) ◽  
pp. 2096-2100 ◽  
Author(s):  
M. Teboul ◽  
E. Enmark ◽  
Q. Li ◽  
A. C. Wikstrom ◽  
M. Pelto-Huikko ◽  
...  

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.


2007 ◽  
Vol 18 (10) ◽  
pp. 3941-3951 ◽  
Author(s):  
Jihui Qiu ◽  
Ying Huang ◽  
Guoqiang Chen ◽  
Zhu Chen ◽  
David J. Tweardy ◽  
...  

Acute promyelocytic leukemia (APL) is characterized by specific chromosomal translocations, which generate fusion proteins such as promyelocytic leukemia (PML)-retinoic acid receptor (RAR)α and promyelocytic leukemia zinc finger (PLZF)-RARα (X-RARα). In this study, we have applied lac operator array systems to study the effects of X-RARα versus wild-type RARα on large-scale chromatin structure. The targeting of these enhanced cyan fluorescent protein-lac repressor-tagged RARα-containing proteins to the gene-amplification chromosomal region by lac operator repeats led to local chromatin condensation, recruitment of nuclear receptor corepressor, and histone deacetylase complex. The addition of retinoic acid (RA) induced large-scale chromatin decondensation in cells expressing RARα; however, cells expressing X-RARα, especially PML-RARα, demonstrated insensitive response to this effect of all-trans retinoic acid (ATRA). Although we did not reveal differences in RA-dependent colocalization of either silencing mediator for retinoid and thyroid or steroid receptor coactivator (SRC)-1 with RARα versus X-RARα, the hormone-independent association between SRC-1 and X-RARα on the array has been identified. Rather, compared with cells expressing RARα, fluorescence recovery after photobleaching of live transfected cells, demonstrated decreased mobility of SRC-1 on the X-RARα–bound chromatin. Thus, the impaired ability of APL fusion proteins to activate gene transcription in response to ATRA corresponds to their reduced ability to remodel chromatin, which may link to their ability to impair the mobility of key nuclear receptor coregulators.


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