Control of secreted protein gene expression and the mammalian secretome by the metabolic regulator PGC-1a
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ABSTRACT: Secreted proteins serve pivotal roles in the development of multicellular organisms, acting as structural matrix, extracellular enzymes and signal molecules. In this study we demonstrate, unexpectedly, that PGC-1α, a critical transcriptional co-activator of metabolic gene expression, functions to down-regulate expression of diverse genes encoding secreted molecules and extracellular matrix (ECM) components to modulate the secretome. We show that both endogenous and exogenous PGC-1α down-regulate expression of numerous genes encoding secreted molecules. Mechanistically, results obtained using mRNA stability measurements as well as intronic RNA expression analysis are consistent with a transcriptional effect of PGC-1α on expression of genes encoding secreted proteins. Interestingly, PGC-1α requires the central heat shock response regulator HSF1 to affect some of its targets, and both factors co-reside on several target genes encoding secreted molecules in cells. Finally, using a mass spectrometric analysis of secreted proteins, we demonstrate that PGC-1α modulates the secretome of mouse embryonic fibroblasts (MEFs).
ORGANISM(S): Mus musculus
PROVIDER: GSE87100 | GEO | 2016/12/01
SECONDARY ACCESSION(S): PRJNA343540
REPOSITORIES: GEO
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