A corepressor and chicken ovalbumin upstream promoter transcriptional factor proteins modulate peroxisome proliferator-activated receptor- γ2/retinoid X receptor α-activated transcription from the murine lipoprotein lipase promoter

Claudius E. Robinson, Xiying Wu, Zafar Nawaz, Sergio A. Onãte, Jeffrey M. Gimble

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Complex physiological stimuli differentially regulate the tissue- specific transcription of the lipoprotein lipase (LPL) gene. A conserved DNA recognition element (-171 to -149 bp) within the promoter functions as a transcriptional enhancer when bound by the peroxiSome proliferator-activated receptor-γ2 (PPARγ2)/retinoid X receptor α (RXRα) heterodimer, but serves as a transcriptional silencer in the presence of unidentified double and single stranded DNA-binding proteins. To address this apparent paradox, the current study examined the effect of two classes of candidate comodulatory proteins, COUP-TF (chicken ovalbumin upstream promoter transcriptional factor) and the corepressor SMRT (silencing mediator of retinoic acid receptor and thyroid receptor). The expression of COUP-TF was detected by Western and Northern blots in a preadipocyte 3T3-L1 cell model during periods corresponding to increased LPL transcription. Cotransfection of COUP-TF expression constructs in the renal epithelial 293T cell line significantly increased transcription from the LPL promoter in synergy with PPARγ2/RXRα, heterodimers. The COUP-TFII (ARP-1) protein specifically bound the LPL PPAR recognition element in electromobility shift assays and interacted directly with the ligand-binding domain of PPARγ in pull-down experiments. In contrast, cotransfection of SMRT repressed PPARγ2/RXRα- mediated LPL transcription in the absence or presence of COUP-TFII (ARP-1). The interaction between PPARγ2 and SMRT localized to the receptor- interactive domain 2 (amino acids 12601495) of the SMRT protein based on cotransfection and pull-down assays. These in vitro data indicate that COUP- TF proteins and SMRT modulate PPARγ-mediated LPL transcription in the 293T cell line.

Original languageEnglish
Pages (from-to)1586-1593
Number of pages8
JournalEndocrinology
Volume140
Issue number4
StatePublished - Apr 8 1999
Externally publishedYes

Fingerprint

Retinoid X Receptors
Co-Repressor Proteins
Peroxisome Proliferator-Activated Receptors
Lipoprotein Lipase
Ovalbumin
Chickens
Proteins
HEK293 Cells
COUP Transcription Factors
3T3-L1 Cells
Cell Line
Retinoic Acid Receptors
DNA
DNA-Binding Proteins
Northern Blotting
Thyroid Gland
Western Blotting
Epithelial Cells
Ligands
Kidney

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

A corepressor and chicken ovalbumin upstream promoter transcriptional factor proteins modulate peroxisome proliferator-activated receptor- γ2/retinoid X receptor α-activated transcription from the murine lipoprotein lipase promoter. / Robinson, Claudius E.; Wu, Xiying; Nawaz, Zafar; Onãte, Sergio A.; Gimble, Jeffrey M.

In: Endocrinology, Vol. 140, No. 4, 08.04.1999, p. 1586-1593.

Research output: Contribution to journalArticle

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abstract = "Complex physiological stimuli differentially regulate the tissue- specific transcription of the lipoprotein lipase (LPL) gene. A conserved DNA recognition element (-171 to -149 bp) within the promoter functions as a transcriptional enhancer when bound by the peroxiSome proliferator-activated receptor-γ2 (PPARγ2)/retinoid X receptor α (RXRα) heterodimer, but serves as a transcriptional silencer in the presence of unidentified double and single stranded DNA-binding proteins. To address this apparent paradox, the current study examined the effect of two classes of candidate comodulatory proteins, COUP-TF (chicken ovalbumin upstream promoter transcriptional factor) and the corepressor SMRT (silencing mediator of retinoic acid receptor and thyroid receptor). The expression of COUP-TF was detected by Western and Northern blots in a preadipocyte 3T3-L1 cell model during periods corresponding to increased LPL transcription. Cotransfection of COUP-TF expression constructs in the renal epithelial 293T cell line significantly increased transcription from the LPL promoter in synergy with PPARγ2/RXRα, heterodimers. The COUP-TFII (ARP-1) protein specifically bound the LPL PPAR recognition element in electromobility shift assays and interacted directly with the ligand-binding domain of PPARγ in pull-down experiments. In contrast, cotransfection of SMRT repressed PPARγ2/RXRα- mediated LPL transcription in the absence or presence of COUP-TFII (ARP-1). The interaction between PPARγ2 and SMRT localized to the receptor- interactive domain 2 (amino acids 12601495) of the SMRT protein based on cotransfection and pull-down assays. These in vitro data indicate that COUP- TF proteins and SMRT modulate PPARγ-mediated LPL transcription in the 293T cell line.",
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