STANDARD_NAME	WANG_TNF_TARGETS
SYSTEMATIC_NAME	M2308
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WANG_TNF_TARGETS
NAMESPACE	MOUSE_SEQ_ACCESSION
DESCRIPTION_BRIEF	Representative genes up-regulated in MEF cells (embryonic fibroblast) in response to TNF [GeneID=7124].
DESCRIPTION_FULL	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.
PMID	17438126
GEOID	
AUTHORS	Wang H,Hertlein E,Bakkar N,Sun H,Acharyya S,Wang J,Carathers M,Davuluri R,Guttridge DC
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 2
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AB051897,NM_001037801,NM_008185,NM_008607,NM_008716,NM_008988,NM_009397,NM_009421,NM_009537,NM_009853,NM_009969,NM_009971,NM_010591,NM_010717,NM_010809,NM_011315,NM_011345,NM_011347,NM_011693,NM_011819,NM_013479,NM_013591,NM_016880,NM_018882,NM_020529,NM_031168
GENE_SYMBOLS	CCL5,CD6,GSTT1,MMP13,NOTCH3,IGDCC3,TNFAIP3,TRAF1,YY1,CD68,CSF2,CSF3,JUN,LIMK1,MMP3,,SELE,SELP,VCAM1,GDF15,BCL2L10,MADCAM1,KRT35,ADGRG1,NFKBIA,IL6
FOUNDER_NAMES