NF-κB mediates the transcription of mouse calsarcin-1 gene, but not calsarcin-2, in C2C12 cellsReport as inadecuate




NF-κB mediates the transcription of mouse calsarcin-1 gene, but not calsarcin-2, in C2C12 cells - Download this document for free, or read online. Document in PDF available to download.

BMC Molecular Biology

, 8:19

First Online: 06 March 2007Received: 22 July 2006Accepted: 06 March 2007

Abstract

BackgroundThe 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.

ResultsOur 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-κB 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-κB 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.

ConclusionOur present data suggest that NF-κB 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2199-8-19 contains supplementary material, which is available to authorized users.

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Author: Heng Wang - Shulin Yang - E Yang - Zhengmao Zhu - Yulian Mu - Shutang Feng - Kui Li

Source: https://link.springer.com/



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