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.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
April 2008
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
March 13 2008
The functional relationship between co-repressor N-CoR and SMRT in mediating transcriptional repression by thyroid hormone receptor α
Kyung-Chul Choi;
Kyung-Chul Choi
*Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
†Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
Search for other works by this author on:
So-Young Oh;
So-Young Oh
‡Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815-26789, U.S.A.
§Program in Gene Function and Expression, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, U.S.A.
Search for other works by this author on:
Hee-Bum Kang;
Hee-Bum Kang
*Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
†Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
Search for other works by this author on:
Yoo-Hyun Lee;
Yoo-Hyun Lee
*Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
Search for other works by this author on:
Seungjoo Haam;
Seungjoo Haam
∥Department of Chemical Engineering, College of Engineering, Yonsei University, Seoul 120-749, South Korea
Search for other works by this author on:
Ha-Il Kim;
Ha-Il Kim
*Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
Search for other works by this author on:
Kunhong Kim;
Kunhong Kim
*Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
†Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
Search for other works by this author on:
Young-Ho Ahn;
Young-Ho Ahn
*Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
†Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
Search for other works by this author on:
Kyung-Sup Kim;
Kyung-Sup Kim
*Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
†Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
Search for other works by this author on:
Ho-Geun Yoon
Ho-Geun Yoon
1
*Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
†Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, 134 Sinchon-dong, Seodaemun-gu, Seoul 120-752, South Korea
1To whom correspondence should be addressed (email [email protected])
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
October 10 2007
Revision Received:
November 28 2007
Accepted:
December 03 2007
Accepted Manuscript online:
December 03 2007
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem J (2008) 411 (1): 19–26.
Article history
Received:
October 10 2007
Revision Received:
November 28 2007
Accepted:
December 03 2007
Accepted Manuscript online:
December 03 2007
Citation
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; The functional relationship between co-repressor N-CoR and SMRT in mediating transcriptional repression by thyroid hormone receptor α. Biochem J 1 April 2008; 411 (1): 19–26. doi: https://doi.org/10.1042/BJ20071393
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |