Human Gene Set: YANG_BCL3_TARGETS_DN


Standard name YANG_BCL3_TARGETS_DN
Systematic name M2425
Brief description Genes down-regulated in neonatal cardiac myocytes upon knockdown of BCL3 [GeneID=602] by RNAi.
Full description or abstract Estrogen-related receptors (ERRs) play critical roles in regulation of cellular energy metabolism in response to inducible coactivators such as peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha (PGC-1alpha). A yeast two-hybrid screen led to the identification of the cytokine-stimulated transcriptional regulator, Bcl3, as an ERRalpha coactivator. Bcl3 was shown to synergize with PGC-1alpha to coactivate ERRalpha. Chromatin immunoprecipitation studies demonstrated that ERRalpha, PGC-1alpha, and Bcl3 form a complex on an ERRalpha-responsive element within the pyruvate dehydrogenase kinase 4 gene promoter in cardiac myocytes. Mapping studies demonstrated that Bc13 interacts with PGC-1alpha and ERRalpha, allowing for interaction with both proteins. Transcriptional profiling demonstrated that Bcl3 activates genes involved in diverse pathways including a subset involved in cellular energy metabolism known to be regulated by PGC-1alpha, ERRalpha, and a second nuclear receptor, PPARalpha. Consistent with the gene expression profiling results, Bcl3 was shown to synergistically coactivate PPARalpha with PGC-1alpha in a manner similar to ERRalpha. We propose that the cooperativity between Bcl3 and PGC-1alpha may serve as a point of convergence on nuclear receptor targets to direct programs orchestrating inflammatory and energy metabolism responses in heart and other tissues.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 19451226   Authors: Yang J,Williams RS,Kelly DP
Exact source Table 3S: Fold change < 1
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Source species Rattus norvegicus
Contributed by Arthur Liberzon (MSigDB Team)
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RAT_SEQ_ACCESSION
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Version history 3.1: First introduced

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