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

Scientific Reports
Ji Suk ChangJ Michael Salbaum

Abstract

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 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 and oxidative metabolism, PGC-1α and NT-PGC-1α additionally target 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-P...Continue Reading

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Citations

Nov 6, 2018·Nature Reviews. Molecular Cell Biology·Matthew J Emmett, Mitchell A Lazar
Jan 29, 2019·Adipocyte·Xiaodan Lu
Oct 28, 2019·Pharmacogenetics and Genomics·Henrik Thyge Corfitsen, Antonio Drago
Feb 14, 2020·Scientific Reports·Meng ZhangNady Golestaneh

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Datasets Mentioned

BETA
GSE110056

Methods Mentioned

BETA
ChIP-seq
immunoprecipitation
ChIP
protein assay

Software Mentioned

DESeq
Genomic Regions Enrichment of Annotations Tool ( GREAT )
DAVID
GSEA
BETA
Gene Set Enrichment Analysis ( GSEA )
SeqPro
Galaxy Cistrome
Bioconductor
Bowtie

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