Gene Set: WANG_NFKB_TARGETS

Standard name WANG_NFKB_TARGETS
Systematic name M2307
Brief description Representative genes up-regulated in C2C12 cells (myoblast) lacking NFkB activity due to expression of a super repressor form of NFKBIA [GeneID=4792].
Full description or abstract NF-kappaB signaling is implicated as an important regulator of skeletal muscle homeostasis, but the mechanisms by which this transcription factor contributes to muscle maturation and turnover remain unclear. To gain insight into these mechanisms, gene expression profiling was examined in C2C12 myoblasts devoid of NF-kappaB activity. Interestingly, even in proliferating myoblasts, the absence of NF-kappaB caused the pronounced induction of several myofibrillar genes, suggesting that NF-kappaB functions as a negative regulator of late-stage muscle differentiation. Although several myofibrillar promoters contain predicted NF-kappaB binding sites, functional analysis using the troponin-I2 gene as a model revealed that NF-kappaB-mediated repression does not occur through direct DNA binding. In the search for an indirect mediator, the transcriptional repressor YinYang1 (YY1) was identified. While inducers of NF-kappaB stimulated YY1 expression in multiple cell types, genetic ablation of the RelA/p65 subunit of NF-kappaB in both cultured cells and adult skeletal muscle correlated with reduced YY1 transcripts and protein. NF-kappaB regulation of YY1 occurred at the transcriptional level, mediated by direct binding of the p50/p65 heterodimer complex to the YY1 promoter. Furthermore, YY1 was found associated with multiple myofibrillar promoters in C2C12 myoblasts containing NF-kappaB activity. Based on these results, we propose that NF-kappaB regulation of YY1 and transcriptional silencing of myofibrillar genes represent a new mechanism by which NF-kappaB functions in myoblasts to modulate skeletal muscle differentiation.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17438126   Authors: Wang H,Hertlein E,Bakkar N,Sun H,Acharyya S,Wang J,Carathers M,Davuluri R,Guttridge DC
Exact source Table 1
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform Mouse_RefSeq
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Version history 3.1: First introduced

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