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A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissue

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE110056 | GEO | 2018/05/22

REPOSITORIES: GEO

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A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissue.

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A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissue [SAGE]

Project description:Transcriptional coactivator PGC-1α and its splice variant NT-PGC-1α play crucial roles in regulating cold-induced thermogenesis in brown adipose tissue (BAT). PGC-1α and NT-PGC-1α are highly induced by cold in BAT and subsequently bind to and coactivate many different transcription factors to regulate expression of genes involved in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis. To identify the complete repertoire of PGC-1α and NT-PGC-1α target genes in BAT, we analyzed genome-wide DNA-binding and gene expression profiles. We find that PGC-1α-/NT-PGC-1α binding broadly associates with cold-mediated transcriptional activation. In addition to their known target genes in mitochondrial biogenesis, fatty acid oxidation, respiration and thermogenesis, PGC-1α and NT-PGC-1α target to a broad spectrum of genes involved in diverse biological pathways including ubiquitin-dependent protein catabolism, ribonucleoprotein complex biosynthesis, phospholipid biosynthesis, angiogenesis, glycogen metabolism, phosphorylation, and autophagy. Our findings expand the number of genes and biological pathways that may be regulated by PGC-1α and NT-PGC-1α and provide further insight into the transcriptional regulatory network in which PGC-1α and NT-PGC-1α coordinate a comprehensive transcriptional response in BAT in response to cold.

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A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissue

Project description:A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissue

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Project description:A map of the PGC-1α- and NT-PGC-1α-regulated transcriptional network in brown adipose tissue [SAGE]

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Remodeling of Brown and White Adipose Tissue by NT-PGC-1α-Mediated Gene Regulation

Project description:The β-adrenergic receptor signaling pathway is a major component of adaptive thermogenesis in brown and white adipose tissue during cold acclimation. The β-AR activation highly induces transcriptional coactivator PGC-1α and its splice variant N-terminal (NT)-PGC-1α, promoting the transcription program of mitochondrial biogenesis and thermogenesis. In the present study, we evaluated the role of NT-PGC-1α in brown adipocyte energy metabolism by genome-wide profiling of NT-PGC-1α-responsive genes. Canonical pathway analysis revealed that a number of genes upregulated by NT-PGC-1α are highly enriched in mitochondrial pathways including fatty acid transport and β-oxidation, TCA cycle and electron transport system, thus reinforcing the crucial role of NT-PGC-1α in the enhancement of mitochondrial function. Moreover, gene expression profiling of NT-PGC-1α revealed activation of distinct metabolic pathways such as glucose, lipid and nucleotide metabolism and of signaling pathways such as RAR and PPAR-γ/RXRα activation in brown adipocytes. Together, our data strengthen our previous findings that NT-PGC-1α is a key regulator of mitochondrial oxidative metabolism and thermogenesis in brown adipocytes and further suggest that NT-PGC-1α influences a broader spectrum of thermogenic processes to meet cellular needs for adaptive thermogenesis. Two samples from two groups: NT-PGC-1α overexpression and empty vector. There are technical replicates (A and B) for each group. Two RNA samples were pooled for each group.

2015-08-07 | E-GEOD-71774 | biostudies-arrayexpress

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