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The functional relationship between co-repressor N-CoR and SMRT in mediating transcriptional repression by thyroid hormone receptor alpha.

 Kyung-Chul CHOI  ;  So-Young OH  ;  Hee-Bum KANG  ;  Yoo-Hyun LEE  ;  Seungjoo HAAM  ;  Ha-Il KIM  ;  Kunhong KIM  ;  Young-Ho AHN  ;  Kyung-Sup KIM  ;  Ho-Geun YOON 
 BIOCHEMICAL JOURNAL, Vol.411(1) : 19-26, 2008 
Journal Title
Issue Date
DNA-Binding Proteins/physiology* ; Fatty Acid Synthases/genetics ; HeLa Cells ; Humans ; Immunoprecipitation ; Nuclear Proteins/genetics ; Nuclear Proteins/physiology* ; Nuclear Receptor Co-Repressor 1 ; Nuclear Receptor Co-Repressor 2 ; Proto-Oncogene Proteins/genetics ; RNA, Small Interfering/genetics ; RNA, Small Interfering/pharmacology ; Repressor Proteins/physiology* ; Response Elements ; Thyroid Hormone Receptors alpha/genetics* ; Transcription Factors/genetics ; Transcription, Genetic* ; Transfection
co-repressor ; nuclear receptor co-repressor (N-CoR) ; repression ; silencing mediator of retinoid and thyroid hormone receptor (SMRT) ; thyroid hormone receptor α
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 (beta-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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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Ha Il(김하일)
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Choi, Kyung Chul(최경철)
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