title: NF-kappaB mediates the transcription of mouse calsarcin-1 gene, but not calsarcin-2, in C2C12 cells.
abstract: BACKGROUND
  The calsarcins comprise a novel family of muscle-specific calcineurin-interaction proteins that play an important role in modulating both the function and substrate specificity of calcineurin in muscle cells. The expression of calsarcin-1 (CS-1) is restricted to slow-twitch skeletal muscle fibres, whereas that of both calsarcin-2 (CS-2) and calsarcin-3 (CS-3) is enriched in fast-twitch fibres. However, the transcriptional control of this selective expression has not been previously elucidated.
  
  
  RESULTS
  Our real-time RT-PCR analyses suggest that the expression of CS-1 and CS-2 is increased during the myogenic differentiation of mouse C2C12 cells. Promoter deletion analysis further suggests that an NF-kappaB binding site within the CS-1 promoter is responsible for the up-regulation of CS-1 transcription, but no similar mechanism was evident for CS-2. These findings are further supported by the results of EMSA analysis, as well as by overexpression and inhibition experiments in which NF-kappaB function was blocked by treatment with its inhibitor, PDTC. In addition, the overexpression of NFATc4 induces both the CS-1 and CS-2 promoters, whereas MEF2C only activates CS-1.
  
  
  CONCLUSIONS
  Our present data suggest that NF-kappaB is required for the transcription of mouse CS-1 but not CS-2, and that the regulation of the calsarcins is mediated also by the NFAT and MEF2 transcription factors. These results provide new insights into the molecular mechanisms governing transcription in specific muscle fibre cells. The calsarcins may also serve as a valuable mechanistic tool to better understand the regulation of calcineurin signalling during muscle differentiation.
authors.affiliation: Department of Gene and Cell Engineering, State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, PR China. muwhy@hotmail.com <muwhy@hotmail.com>
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.forename: Shulin
authors.initials: S
authors.lastname: Yang
authors.forename: E
authors.initials: E
authors.lastname: Yang
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Zhu
authors.forename: Yulian
authors.initials: Y
authors.lastname: Mu
authors.forename: Shutang
authors.initials: S
authors.lastname: Feng
authors.forename: Kui
authors.initials: K
authors.lastname: Li
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D051379:Mice; D008840:Microfilament Proteins; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D032446:Myoblasts / Q000502:physiology; D018006:Myogenic Regulatory Factors / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D011759:Pyrrolidines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology; D024363:Transcription Initiation Site / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; C523647:Myoz1 protein, mouse; C523646:Myoz2 protein, mouse; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid