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Series GSE75448 Query DataSets for GSE75448
Status Public on Jun 07, 2016
Title Peroxisome proliferator-activated receptor gamma coactivator-1alpha isoforms selectively regulate multiple splicing events on target genes.
Organism Mus musculus
Experiment type Expression profiling by array
Summary Endurance and resistance exercise training induce specific and profound changes in the skeletal muscle transcriptome. PGC-1a; coactivators are not only among the genes differentially induced by distinct training methods, but also participate in the ensuing signaling cascades that allow skeletal muscle to adapt to each type of exercise. While endurance training preferentially induces PGC-1a1 expression, resistance exercise activates the expression of PGC-1a2, a3, and a4. These three alternative PGC-1a isoforms lack the arginine-serine (RS) and RNA Recognition Motifs (RRM) characteristic of PGC-1a1. Discrete functions for PGC-1a1 and a4 have been described, but the biological role of PGC-1a2 and a3 remains elusive. Here we show that different PGC-1a variants can affect target gene splicing through diverse mechanisms, including alternative promoter usage. By analyzing the exon structure of the target transcripts for each PGC-1a isoform, we were able to identify a large number of previously unknown PGC-1a2 and a3 target genes and pathways in skeletal muscle. In particular, PGC-1a2 seems to mediate a decrease in the levels of cholesterol synthesis genes. Our results suggest that the conservation of the N-terminal activation and repression domains (and not the RS/RRM) is what determines the gene programs and splicing options modulated by each PGC-1a isoform. By using skeletal muscle-specific transgenics for PGC-1a1 and a4, we could validate in vivo splicing events observed in in vitro studies. These results show that alternative PGC-1a variants can affect target gene expression both quantitatively and qualitatively, and identify novel biological pathways under the control of this system of coactivators.
Overall design Gene expression profiling after activation by PGC-1a1, PGC-1a2, PGC-1a3 or PGC-1a4. GFP expression was used as a control.
Web link
Contributor(s) Martínez-Redondo V, Jannig P, Lindvall JM, Sinha I, Cervenka I, Correia JC, Izadi M, Pettersson-Klein AT, Agudelo LZ, Gimenez-Cassina A, Brum PC, Ferreira DM, Dahlman-Wright K, Ruas JL
Citation(s) 27231350
Submission date Nov 27, 2015
Last update date Mar 06, 2018
Contact name Karin Dahlman-Wright
Organization name Karolinska Institutet
Department Department of Biosciences and Nutrition
Lab Medicinaren 25/Neo
Street address Blickagången 16
City Huddinge
ZIP/Postal code 14157
Country Sweden
Platforms (1)
GPL6096 [MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [transcript (gene) version]
Samples (15)
GSM1955354 GFP 1
GSM1955355 GFP 2
GSM1955356 GFP 3
BioProject PRJNA304309

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Supplementary file Size Download File type/resource
GSE75448_RAW.tar 327.0 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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