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A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type.

Publication ,  Journal Article
Chin, ER; Olson, EN; Richardson, JA; Yang, Q; Humphries, C; Shelton, JM; Wu, H; Zhu, W; Bassel-Duby, R; Williams, RS
Published in: Genes Dev
August 15, 1998

Slow- and fast-twitch myofibers of adult skeletal muscles express unique sets of muscle-specific genes, and these distinctive programs of gene expression are controlled by variations in motor neuron activity. It is well established that, as a consequence of more frequent neural stimulation, slow fibers maintain higher levels of intracellular free calcium than fast fibers, but the mechanisms by which calcium may function as a messenger linking nerve activity to changes in gene expression in skeletal muscle have been unknown. Here, fiber-type-specific gene expression in skeletal muscles is shown to be controlled by a signaling pathway that involves calcineurin, a cyclosporin-sensitive, calcium-regulated serine/threonine phosphatase. Activation of calcineurin in skeletal myocytes selectively up-regulates slow-fiber-specific gene promoters. Conversely, inhibition of calcineurin activity by administration of cyclosporin A to intact animals promotes slow-to-fast fiber transformation. Transcriptional activation of slow-fiber-specific transcription appears to be mediated by a combinatorial mechanism involving proteins of the NFAT and MEF2 families. These results identify a molecular mechanism by which different patterns of motor nerve activity promote selective changes in gene expression to establish the specialized characteristics of slow and fast myofibers.

Duke Scholars

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Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

August 15, 1998

Volume

12

Issue

16

Start / End Page

2499 / 2509

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • Transcription Factors
  • Signal Transduction
  • Rats
  • Promoter Regions, Genetic
  • Nuclear Proteins
  • NFATC Transcription Factors
  • Muscle, Skeletal
  • Muscle Fibers, Slow-Twitch
 

Citation

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Chin, E. R., Olson, E. N., Richardson, J. A., Yang, Q., Humphries, C., Shelton, J. M., … Williams, R. S. (1998). A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev, 12(16), 2499–2509. https://doi.org/10.1101/gad.12.16.2499
Chin, E. R., E. N. Olson, J. A. Richardson, Q. Yang, C. Humphries, J. M. Shelton, H. Wu, W. Zhu, R. Bassel-Duby, and R. S. Williams. “A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type.Genes Dev 12, no. 16 (August 15, 1998): 2499–2509. https://doi.org/10.1101/gad.12.16.2499.
Chin ER, Olson EN, Richardson JA, Yang Q, Humphries C, Shelton JM, et al. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev. 1998 Aug 15;12(16):2499–509.
Chin, E. R., et al. “A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type.Genes Dev, vol. 12, no. 16, Aug. 1998, pp. 2499–509. Pubmed, doi:10.1101/gad.12.16.2499.
Chin ER, Olson EN, Richardson JA, Yang Q, Humphries C, Shelton JM, Wu H, Zhu W, Bassel-Duby R, Williams RS. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev. 1998 Aug 15;12(16):2499–2509.

Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

August 15, 1998

Volume

12

Issue

16

Start / End Page

2499 / 2509

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription, Genetic
  • Transcription Factors
  • Signal Transduction
  • Rats
  • Promoter Regions, Genetic
  • Nuclear Proteins
  • NFATC Transcription Factors
  • Muscle, Skeletal
  • Muscle Fibers, Slow-Twitch