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Dev Biol. 2008 Dec 15;324(2):226-35. doi: 10.1016/j.ydbio.2008.09.020. Epub 2008 Sep 27.

Specification of vertebrate slow-twitch muscle fiber fate by the transcriptional regulator Blimp1.

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  • 1Institute of Molecular and Cell Biology, Cancer and Developmental Cell Biology Division, Proteos, 61 Biopolis Drive, Singapore 138673, Singapore.

Erratum in

  • Dev Biol. 2009 May 1;329(1):167.

Abstract

Skeletal muscles of vertebrates are typically composed of slow- and fast-twitch fibers that differ in their morphology, gene expression profiles, contraction speeds, metabolic properties and patterns of innervation. During myogenesis, how muscle precursors are induced to mature into distinct slow- or fast-twitch fiber-types is inadequately understood. We have previously shown that within the somites of the zebrafish embryo, the activity of the zinc finger and SET domain-containing transcriptional regulator Blimp1 is essential for the specification of slow muscle fibers. Here, we have investigated the mechanism by which Blimp1 programs myoblasts to adopt the slow-twitch fiber fate. In slow myoblasts, expression of the Blimp1 protein is transient, and precedes the expression of slow muscle-specific differentiation genes. We demonstrate that the competence of somitic myoblasts to commit to the slow lineage in response to Blimp1 changes as a function of developmental time. Furthermore, we provide evidence that mammalian Blimp1 can recapitulate the slow myogenic program in zebrafish, suggesting that zebrafish Blimp1 can recognize the same consensus DNA sequence that is bound by the mammalian protein. Finally, we show that zebrafish Blimp1 can repress the expression of fast muscle-specific myosin light chain, mylz2, through direct binding near the promoter of this gene, indicating that an important function of the transcriptional activity of Blimp1 in slow muscle development is the suppression of fast muscle-specific gene expression. Taken together, these findings provide new insights into the molecular basis of vertebrate muscle fiber-type specification, and underscore Blimp1 as the central determinant of this process.

PMID:
18948093
DOI:
10.1016/j.ydbio.2008.09.020
[PubMed - indexed for MEDLINE]
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