Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade.

Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade. Research Abstract Details 

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Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade. Abstract Text:

Huibin Tang,Daniel Goldman,

Muscle activity contributes to muscle development and function largely by means of regulated gene expression. Many genes crucial to neuromuscular synapse formation, such as MuSK and nAChRs, are induced before muscle innervation or after muscle denervation, and this induction requires expression of the E-box binding, basic helix-loop-helix muscle-specific transcription factor, myogenin (Mgn). The mechanism by which muscle activity is coupled to gene expression is poorly defined. Here we report that inhibition of histone deacetylase (HDAC) activity attenuates the induction of activity-regulated genes in aneural myotubes and adult denervated muscle. The effect of HDAC inhibitors requires new protein synthesis, suggesting HDACs may regulate the expression of a Mgn transcriptional repressor. We identified Dach2 as a Mgn transcriptional repressor whose expression is dramatically reduced in an HDAC-dependent manner in developing aneural myotubes or adult denervated muscle. Dach2 overexpression in denervated muscle suppressed Mgn, nAChR, and MuSK gene induction, whereas Dach2 knockdown induced Mgn gene expression in innervated muscle and relieved Mgn promoter inhibition by HDAC inhibitors. Thus, a HDAC-Dach2-myogenin signaling pathway has been identified to decode nerve activity and control muscle gene expression in developing and adult skeletal muscle.

Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade. Publishing Authors By Initials

H Tang,D Goldman,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 16977-82

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 30

MONTH: 10

YEAR: 2006

Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: genetics

Chemical & Substance for Abstract: Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade. Information

Substance Name: Histone Deacetylases

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for Activity-dependent gene regulation in skeletal muscle is mediated by a histone deacetylase (HDAC)-Dach2-myogenin signal transduction cascade.

AFFILIATION: Molecular and Behavioral Neuroscience Institute and Department of Biological Chemistry, 109 Zina Pitcher Place, University of Michigan, Ann Arbor, MI 48109, USA.

Country: United States

AGENCY: United States NINDS

GRANT: 5R01 NS 025153

ACRONYM: NS

MEDLINETA: Proc Natl Acad Sci U S A

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