title: TEAD1-dependent expression of the FoxO3a gene in mouse skeletal muscle.
abstract: BACKGROUND
  TEAD1 (TEA domain family member 1) is constitutively expressed in cardiac and skeletal muscles. It acts as a key molecule of muscle development, and trans-activates multiple target genes involved in cell proliferation and differentiation pathways. However, its target genes in skeletal muscles, regulatory mechanisms and networks are unknown.
  
  
  RESULTS
  In this paper, we have identified 136 target genes regulated directly by TEAD1 in skeletal muscle using integrated analyses of ChIP-on-chip. Most of the targets take part in the cell process, physiology process, biological regulation metabolism and development process. The targets also play an important role in MAPK, mTOR, T cell receptor, JAK-STAT, calcineurin and insulin signaling pathways. TEAD1 regulates foxo3a transcription through binding to the M-CAT element in foxo3a promoter, demonstrated with independent ChIP-PCR, EMSA and luciferase reporter system assay. In addition, results of over-expression and inhibition experiments suggest that foxo3a is positively regulated by TEAD1.
  
  
  CONCLUSIONS
  Our present data suggests that TEAD1 plays an important role in the regulation of gene expression and different signaling pathways may co-operate with each other mediated by TEAD1. We have preliminarily concluded that TEAD1 may regulate FoxO3a expression through calcineurin/MEF2/NFAT and IGF-1/PI3K/AKT signaling pathways in skeletal muscles. These findings provide important clues for further analysis of the role of FoxO3a gene in the formation and transformation of skeletal muscle fiber types.
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Haifang
authors.initials: H
authors.lastname: Qiu
authors.forename: Fengli
authors.initials: F
authors.lastname: Wang
authors.forename: Chuxin
authors.initials: C
authors.lastname: Liu
authors.forename: Xuewen
authors.initials: X
authors.lastname: Xu
authors.forename: Bang
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D001483:Base Sequence; D019703:Calcineurin / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D034741:RNA, Small Interfering; D000091262:TEA Domain Transcription Factors; C083215:Tead1 protein, mouse; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D019703:Calcineurin