Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

PGC-1 alpha isoforms and muscle hypertrophy

ABSTRACT: An alternative promoter of the PGC-1 alpha gene gives arrise to 3 new isofroms of the PGC-1 alpha gene refered to as PGC-1a2 (A2), PGC-1a3 (A3) and PGC-1a4 (A4). The proximal PGC-1 alpha promotor transcribes the canonical PGC-1 alpha which is refered to as PGC-1a1 (A1).G1/G2/G3 samples refer to the Green fluorescent protein (GFP) control samples used in this experiment. Forced expression of specifically PGC-1a4 isoform results in muslce hypertrophy associated with increased IGF-1 signaling and repression of myostatin signaling. Adnoviral over expression assays were performed on primary myoblasts from C57BL/6 mice for each of the PGC-1 alpha isoforms originating from the proximal or alternative promotor.

ORGANISM(S): Mus musculus

SUBMITTER: Bruce Spiegelman

PROVIDER: E-GEOD-42473 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:PGC-1a is a transcriptional coactivator known to regulate a broad gene program of nutrient and mitochondrial metabolism. Many splice variants of this protein have been identified, but their functions were unknown. This experiment was designed to delineate the downstream targets of two different PGC-1alpha isoforms (PGC-1a1 and PGC-1a4) in hepatocytes, and to determine whether inflammatory signaling (via TNFR activation) modulated these targets Liver is exposed to constantly changing metabolic and inflammatory environments. It must quickly sense and adapt to metabolic need while balancing resources required to protect itself from harmful inflammatory molecules. PGC-1α is a transcriptional coactivator that mediates cellular adaptation to diverse stimuli including inflammation. PGC-1α has a protective role against inflammation in several organs, including brain, heart, kidney, muscle, and liver. However, it is not known how hepatic PGC-1α integrates extracellular signals to mitigate inflammatory outcomes. PGC-1α exists as multiple, alternatively spliced variants whose expression is differentially regulated by different gene promoters. In human liver, we found that inflammatory conditions preferentially activated the alternative versus proximal PPARGC1A promoter. Gene expression analysis performed in primary mouse hepatocytes identified many shared and isoform-specific roles for PGC-1α variants during acute inflammation. PGC-1α1 primarily impacted gene programs of nutrient and mitochondrial metabolism, while TNFα treatment revealed that PGC-1α4 uniquely influenced several pathways related to innate immunity and cell death. Gain- and loss-of-function models showed that PGC-1α4 specifically attenuated apoptosis in response to TNFα or LPS, in contrast to PGC-1α1, which reduced expression of a wide inflammatory gene network. We conclude that PGC-1α variants have distinct, yet complimentary roles in hepatic responses to inflammation, with PGC-1α4 being an important mitigator of apoptosis.

Dataset Information

PGC-1 alpha isoforms and muscle hypertrophy

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets