Thyroid Hormone Receptor Alpha Plays an Essential Role in the Normalisation of Adult-Onset Hypothyroidism-Related Hypoexpression of Synaptic Plasticity Target Genes in Striatum

2009 ◽  
Vol 21 (1) ◽  
pp. 49-56 ◽  
Author(s):  
J. Vallortigara ◽  
O. Chassande ◽  
P. Higueret ◽  
V. Enderlin
PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e30703 ◽  
Author(s):  
Fabrice Chatonnet ◽  
Romain Guyot ◽  
Frédéric Picou ◽  
Maria Bondesson ◽  
Frederic Flamant

2008 ◽  
Vol 411 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Kyung-Chul Choi ◽  
So-Young Oh ◽  
Hee-Bum Kang ◽  
Yoo-Hyun Lee ◽  
Seungjoo Haam ◽  
...  

A central issue in mediating repression by nuclear hormone receptors is the distinct or redundant function between co-repressors N-CoR (nuclear receptor co-repressor) and SMRT (silencing mediator of retinoid and thyroid hormone receptor). To address the functional relationship between SMRT and N-CoR in TR (thyroid hormone receptor)-mediated repression, we have identified multiple TR target genes, including BCL3 (B-cell lymphoma 3-encoded protein), Spot14 (thyroid hormone-inducible hepatic protein), FAS (fatty acid synthase), and ADRB2 (β-adrenergic receptor 2). We demonstrated that siRNA (small interfering RNA) treatment against either N-CoR or SMRT is sufficient for the de-repression of multiple TR target genes. By the combination of sequence mining and physical association as determined by ChIP (chromatin immunoprecipitation) assays, we mapped the putative TREs (thyroid hormone response elements) in BCL3, Spot14, FAS and ADRB2 genes. Our data clearly show that SMRT and N-CoR are independently recruited to various TR target genes. We also present evidence that overexpression of N-CoR can restore repression of endogenous genes after knocking down SMRT. Finally, unliganded, co-repressor-free TR is defective in repression and interacts with a co-activator, p300. Collectively, these results suggest that both SMRT and N-CoR are limited in cells and that knocking down either of them results in co-repressor-free TR and consequently de-repression of TR target genes.


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