Transcriptional Activity of PGC-1α and NT-PGC-1α Is Differentially Regulated by Twist-1 in Brown Fat Metabolism
Brown fat expresses two PGC-1α isoforms (PGC-1α and NT-PGC-1α) and both play a central role in the regulation of cellular energy metabolism and adaptive thermogenesis by interacting with a wide range of transcription factors including PPARγ, PPARα, ERRα, and NRF1. PGC-1α consists of 797 amino acids,...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2012/320454 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832549365702459392 |
|---|---|
| author | Hee-Jin Jun Thomas W. Gettys Ji Suk Chang |
| author_facet | Hee-Jin Jun Thomas W. Gettys Ji Suk Chang |
| author_sort | Hee-Jin Jun |
| collection | DOAJ |
| description | Brown fat expresses two PGC-1α isoforms (PGC-1α and NT-PGC-1α) and both play a central role in the regulation of cellular energy metabolism and adaptive thermogenesis by interacting with a wide range of transcription factors including PPARγ, PPARα, ERRα, and NRF1. PGC-1α consists of 797 amino acids, whereas alternative splicing of the PGC-1α gene produces a shorter protein called NT-PGC-1α (aa 1–270). We report in this paper that transcriptional activity of PGC-1α and NT-PGC-1α is differently affected by the transcriptional regulator, Twist-1. Twist-1 suppresses PGC-1α but not NT-PGC-1α. The inhibition of PGC-1α activity by Twist-1 is mediated by direct interaction through the C-terminal region of PGC-1α (aa 353–797). Thus, the absence of the corresponding C-terminal domain in NT-PGC-1α allows NT-PGC-1α to be free from Twist-1-mediated inhibition. Overexpression of Twist-1 in brown adipocytes suppresses transcription of a subset of PGC-1α-target genes involved in mitochondrial fatty acid oxidation and uncoupling (CPT1β, UCP1, and ERRα). In contrast, NT-PGC-1α-mediated induction of these genes is unaffected by Twist-1. These findings show that differences in inhibitory protein-protein interactions of PGC-1α and NT-PGC-1α with Twist-1 lead to differential regulation of their function by Twist-1. |
| format | Article |
| id | doaj-art-33a0316af5b74b63a5a060edf65c3eed |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-33a0316af5b74b63a5a060edf65c3eed2025-02-03T06:11:27ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/320454320454Transcriptional Activity of PGC-1α and NT-PGC-1α Is Differentially Regulated by Twist-1 in Brown Fat MetabolismHee-Jin Jun0Thomas W. Gettys1Ji Suk Chang2Laboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USALaboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USALaboratory of Nutrient Sensing and Adipocyte Signaling, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USABrown fat expresses two PGC-1α isoforms (PGC-1α and NT-PGC-1α) and both play a central role in the regulation of cellular energy metabolism and adaptive thermogenesis by interacting with a wide range of transcription factors including PPARγ, PPARα, ERRα, and NRF1. PGC-1α consists of 797 amino acids, whereas alternative splicing of the PGC-1α gene produces a shorter protein called NT-PGC-1α (aa 1–270). We report in this paper that transcriptional activity of PGC-1α and NT-PGC-1α is differently affected by the transcriptional regulator, Twist-1. Twist-1 suppresses PGC-1α but not NT-PGC-1α. The inhibition of PGC-1α activity by Twist-1 is mediated by direct interaction through the C-terminal region of PGC-1α (aa 353–797). Thus, the absence of the corresponding C-terminal domain in NT-PGC-1α allows NT-PGC-1α to be free from Twist-1-mediated inhibition. Overexpression of Twist-1 in brown adipocytes suppresses transcription of a subset of PGC-1α-target genes involved in mitochondrial fatty acid oxidation and uncoupling (CPT1β, UCP1, and ERRα). In contrast, NT-PGC-1α-mediated induction of these genes is unaffected by Twist-1. These findings show that differences in inhibitory protein-protein interactions of PGC-1α and NT-PGC-1α with Twist-1 lead to differential regulation of their function by Twist-1.http://dx.doi.org/10.1155/2012/320454 |
| spellingShingle | Hee-Jin Jun Thomas W. Gettys Ji Suk Chang Transcriptional Activity of PGC-1α and NT-PGC-1α Is Differentially Regulated by Twist-1 in Brown Fat Metabolism PPAR Research |
| title | Transcriptional Activity of PGC-1α and NT-PGC-1α Is Differentially Regulated by Twist-1 in Brown Fat Metabolism |
| title_full | Transcriptional Activity of PGC-1α and NT-PGC-1α Is Differentially Regulated by Twist-1 in Brown Fat Metabolism |
| title_fullStr | Transcriptional Activity of PGC-1α and NT-PGC-1α Is Differentially Regulated by Twist-1 in Brown Fat Metabolism |
| title_full_unstemmed | Transcriptional Activity of PGC-1α and NT-PGC-1α Is Differentially Regulated by Twist-1 in Brown Fat Metabolism |
| title_short | Transcriptional Activity of PGC-1α and NT-PGC-1α Is Differentially Regulated by Twist-1 in Brown Fat Metabolism |
| title_sort | transcriptional activity of pgc 1α and nt pgc 1α is differentially regulated by twist 1 in brown fat metabolism |
| url | http://dx.doi.org/10.1155/2012/320454 |
| work_keys_str_mv | AT heejinjun transcriptionalactivityofpgc1aandntpgc1aisdifferentiallyregulatedbytwist1inbrownfatmetabolism AT thomaswgettys transcriptionalactivityofpgc1aandntpgc1aisdifferentiallyregulatedbytwist1inbrownfatmetabolism AT jisukchang transcriptionalactivityofpgc1aandntpgc1aisdifferentiallyregulatedbytwist1inbrownfatmetabolism |