NFATc1 Controls Skeletal Muscle Fiber Type and Is a Negative Regulator of MyoD Activity
Skeletal muscle comprises a heterogeneous population of fibers with important physiological differences. Fast fibers are glycolytic and fatigue rapidly. Slow fibers utilize oxidative metabolism and are fatigue resistant. Muscle diseases such as sarcopenia and atrophy selectively affect fast fibers,...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714007116 |
| _version_ | 1828920585279766528 |
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| author | Melissa L. Ehlers Barbara Celona Brian L. Black |
| author_facet | Melissa L. Ehlers Barbara Celona Brian L. Black |
| author_sort | Melissa L. Ehlers |
| collection | DOAJ |
| description | Skeletal muscle comprises a heterogeneous population of fibers with important physiological differences. Fast fibers are glycolytic and fatigue rapidly. Slow fibers utilize oxidative metabolism and are fatigue resistant. Muscle diseases such as sarcopenia and atrophy selectively affect fast fibers, but the molecular mechanisms regulating fiber type-specific gene expression remain incompletely understood. Here, we show that the transcription factor NFATc1 controls fiber type composition and is required for fast-to-slow fiber type switching in response to exercise in vivo. Moreover, MyoD is a crucial transcriptional effector of the fast fiber phenotype, and we show that NFATc1 inhibits MyoD-dependent fast fiber gene promoters by physically interacting with the N-terminal activation domain of MyoD and blocking recruitment of the essential transcriptional coactivator p300. These studies establish a molecular mechanism for fiber type switching through direct inhibition of MyoD to control the opposing roles of MyoD and NFATc1 in fast versus slow fiber phenotypes. |
| first_indexed | 2024-12-13T21:48:23Z |
| format | Article |
| id | doaj.art-6113227820e44375b858c0d38defce34 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T21:48:23Z |
| publishDate | 2014-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6113227820e44375b858c0d38defce342022-12-21T23:30:21ZengElsevierCell Reports2211-12472014-09-01861639164810.1016/j.celrep.2014.08.035NFATc1 Controls Skeletal Muscle Fiber Type and Is a Negative Regulator of MyoD ActivityMelissa L. Ehlers0Barbara Celona1Brian L. Black2Cardiovascular Research Institute, University of California, San Francisco, CA 94158-2517, USACardiovascular Research Institute, University of California, San Francisco, CA 94158-2517, USACardiovascular Research Institute, University of California, San Francisco, CA 94158-2517, USASkeletal muscle comprises a heterogeneous population of fibers with important physiological differences. Fast fibers are glycolytic and fatigue rapidly. Slow fibers utilize oxidative metabolism and are fatigue resistant. Muscle diseases such as sarcopenia and atrophy selectively affect fast fibers, but the molecular mechanisms regulating fiber type-specific gene expression remain incompletely understood. Here, we show that the transcription factor NFATc1 controls fiber type composition and is required for fast-to-slow fiber type switching in response to exercise in vivo. Moreover, MyoD is a crucial transcriptional effector of the fast fiber phenotype, and we show that NFATc1 inhibits MyoD-dependent fast fiber gene promoters by physically interacting with the N-terminal activation domain of MyoD and blocking recruitment of the essential transcriptional coactivator p300. These studies establish a molecular mechanism for fiber type switching through direct inhibition of MyoD to control the opposing roles of MyoD and NFATc1 in fast versus slow fiber phenotypes.http://www.sciencedirect.com/science/article/pii/S2211124714007116 |
| spellingShingle | Melissa L. Ehlers Barbara Celona Brian L. Black NFATc1 Controls Skeletal Muscle Fiber Type and Is a Negative Regulator of MyoD Activity Cell Reports |
| title | NFATc1 Controls Skeletal Muscle Fiber Type and Is a Negative Regulator of MyoD Activity |
| title_full | NFATc1 Controls Skeletal Muscle Fiber Type and Is a Negative Regulator of MyoD Activity |
| title_fullStr | NFATc1 Controls Skeletal Muscle Fiber Type and Is a Negative Regulator of MyoD Activity |
| title_full_unstemmed | NFATc1 Controls Skeletal Muscle Fiber Type and Is a Negative Regulator of MyoD Activity |
| title_short | NFATc1 Controls Skeletal Muscle Fiber Type and Is a Negative Regulator of MyoD Activity |
| title_sort | nfatc1 controls skeletal muscle fiber type and is a negative regulator of myod activity |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714007116 |
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