PPARgamma and C/EBP factors orchestrate adipocyte biology via adjacent binding on a genome-wide scale.

By M. Lefterova, Yong Zhang, D. Steger, M. Schupp, Jonathan Schug, Ana G. Cristancho, Dan Feng, David Zhuo, Christian J. Stoeckert Jr., X. S. Liu and 1 more. Genes & Development, 2008

826 citations recorded by the source corpus.

Peroxisome proliferator-activated receptor gamma(PPARgamma), a nuclear receptor and the target of anti-diabetic thiazolinedione drugs, is known as the master regulator of adipocyte biology. Although it regulates hundreds of adipocyte genes, PPARgamma binding to endogenous genes has rarely been demonstrated. Here, utilizing chromatin immunoprecipitation (ChIP) coupled with whole genome tiling arrays, we identified 5299 genomic regions of PPARgamma binding in mouse 3T3-L1 adipocytes. The consensus PPARgamma/RXRalpha "DR-1"-binding motif was found at most of the sites, and ChIP for RXRalpha showed colocalization at nearly all locations tested. Bioinformatics analysis also revealed CCAAT/enhancer-binding protein (C/EBP)-binding motifs in the vicinity of most PPARgamma-binding sites, and genome-wide analysis of C/EBPalpha binding demonstrated that it localized to 3350 of the locations bound by PPARgamma. Importantly, most genes induced in adipogenesis were bound by both PPARgamma and C/EBPalpha, while very few were PPARgamma-specific. C/EBPbeta also plays a role at many of these genes, such that both C/EBPalpha and beta are required along with PPARgamma for robust adipocyte-specific gene expression. Thus, PPARgamma and C/EBP factors cooperatively orchestrate adipocyte biology by adjacent binding on an unanticipated scale.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/afd0dbb9971d7d080543f1eef3431c955c04b316

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In Molecular Biology

1. S. Kersten
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Citations in the corpus

• CpG methylation of half-CRE sequences creates C/EBPα binding sites that activate some tissue-specific genes (2010, background): “C/EBPα is also known to be important for adipocyte differentiation (21), and we investigated if C/EBPα binding to methylated CpG sequences is critical for differentia-”
• Peroxisome Proliferator-Activated Receptor Alpha Target Genes (2010, background): “[13] M.”
• Forming functional fat: a growing understanding of adipocyte differentiation (2011, background): “, it is the expression of PPARγ, CCAAT/enhancer-binding protein-α (C/EBPα), C/EBPβ and C/EBPδ, as well as the epigenomic coordination between these factors, that are the primary drivers of adipocyte gene induction during terminal differentiatio”
• Adipose Tissue Dysfunction as Determinant of Obesity-Associated Metabolic Complications (2019, background): “These factors cooperatively orchestrate adipocyte biology by adjacent binding sites and establish the mature adipocyte phenotype [72,89].”
• Metabolism Disrupting Chemicals and Metabolic Disorders (2016, neutral): “and -δ [123, 124] which establish a sustained feedback loop.”