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

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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)19-26
Number of pages8
JournalBiochemical Journal
Volume411
Issue number1
DOIs
Publication statusPublished - 2008 Apr 1

Fingerprint

Thyroid Hormone Receptors
Co-Repressor Proteins
Genes
Fatty Acid Synthases
Thyroid Hormones
B-Cell Lymphoma
Proteins
Retinoids
Response Elements
Cytoplasmic and Nuclear Receptors
Chromatin Immunoprecipitation
Adrenergic Receptors
Small Interfering RNA
Chromatin
Assays
Cells
Association reactions

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Choi, Kyung Chul ; Oh, So Young ; Kang, Hee Bum ; Lee, Yoo Hyun ; Haam, Seungjoo ; Kim, Ha Il ; Kim, Kunhong ; Ahn, Young Ho ; Kim, Kyung Sup ; Yoon, Ho Geun. / The functional relationship between co-repressor N-CoR and SMRT in mediating transcriptional repression by thyroid hormone receptor α. In: Biochemical Journal. 2008 ; Vol. 411, No. 1. pp. 19-26.
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The functional relationship between co-repressor N-CoR and SMRT in mediating transcriptional repression by thyroid hormone receptor α. / Choi, Kyung Chul; Oh, So Young; Kang, Hee Bum; Lee, Yoo Hyun; Haam, Seungjoo; Kim, Ha Il; Kim, Kunhong; Ahn, Young Ho; Kim, Kyung Sup; Yoon, Ho Geun.

In: Biochemical Journal, Vol. 411, No. 1, 01.04.2008, p. 19-26.

Research output: Contribution to journalArticle

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T1 - The functional relationship between co-repressor N-CoR and SMRT in mediating transcriptional repression by thyroid hormone receptor α

AU - Choi, Kyung Chul

AU - Oh, So Young

AU - Kang, Hee Bum

AU - Lee, Yoo Hyun

AU - Haam, Seungjoo

AU - Kim, Ha Il

AU - Kim, Kunhong

AU - Ahn, Young Ho

AU - Kim, Kyung Sup

AU - Yoon, Ho Geun

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N2 - 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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