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

Tang, Huibin; Goldman, Daniel

doi:10.1073/pnas.0601565103

Cited by 82 publications

(89 citation statements)

References 38 publications

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“…These intrinsic differences in abundance or activity of such factors presumably would be the result of developmental processes during determination of cell fate (33,34). Alternatively, activitydependent processes may exist that feed back to the transcription factors/miRNAs regulating ion channel gene expression (35)(36)(37). Because each cell type has a unique pattern of activity, these factors presumably would be differentially regulated by these activity-dependent processes, leading to differences in the relationship between channel genes in different cell types.…”

Section: Discussionmentioning

confidence: 99%

Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression

Schulz

Goaillard

Marder

2007

Proc. Natl. Acad. Sci. U.S.A.

286

379

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The postdevelopmental basis of cellular identity and the unique cellular output of a particular neuron type are of particular interest in the nervous system because a detailed understanding of circuits responsible for complex processes in the brain is impeded by the often ambiguous classification of neurons in these circuits. Neurons have been classified by morphological, electrophysiological, and neurochemical techniques. More recently, molecular approaches, particularly microarray, have been applied to the question of neuronal identity. With the realization that proteins expressed exclusively in only one type of neuron are rare, expression profiles obtained from neuronal subtypes are analyzed to search for diagnostic patterns of gene expression. However, this expression profiling hinges on one critical and implicit assumption: that neurons of the same type in different animals achieve their conserved functional output via conserved levels and quantitative relationships of gene expression. Here we exploit the unambiguously identifiable neurons in the crab stomatogastric ganglion to investigate the precise quantitative expression profiling of neurons at the level of single-cell ion channel expression. By measuring absolute mRNA levels of six different channels in the same individually identified neurons, we demonstrate that not only do individual cell types possess highly variable levels of channel expression but that this variability is constrained by unique patterns of correlated channel expression.ion channels ͉ neuronal identity ͉ plasticity ͉ stomatogastric ͉ quantitative PCR A nimals contain many different kinds of neurons that can be superficially described in terms of their anatomical forms, the patterns of connections they make, the neurotransmitters they release, and their electrophysiological properties. In small invertebrate nervous systems, it is relatively easy to identify neurons unambiguously by using one or more of the above attributes. Likewise, certain vertebrate neurons, such as the Mauthner cell in fish and amphibians (1), are unambiguously identifiable, as a function of size and location. In large vertebrate brains with many neurons with similar properties, it can be quite difficult to identify neurons unambiguously, which has significantly impeded efforts to understand the neuronal circuits in larger brains. Consequently, there are now major efforts under way to use a combination of molecular, anatomical, and physiological methods to identify neurons in vertebrate brains and spinal cords (2-4). Nonetheless, it is not yet apparent which combinations of attributes are adequate to define neuronal identity.There is a large literature on the expression of various transcription factors and other genes in determining neuronal identity during development (5-8). However, characterizing the molecular processes that determine the lineage of a cell may not provide sufficient insight into the molecular markers expressed by those neurons many years later, as they function in the adult brain.The electrop...

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Section: Discussionmentioning

confidence: 99%

Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression

Schulz

Goaillard

Marder

2007

Proc. Natl. Acad. Sci. U.S.A.

286

379

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“…The class II HDACs regulate myogenesis via the transcription factor myocyte enhancer factor‐2 (Lu et al ., 2000), and HDAC4 is involved in innervation‐regulated gene transcription (Tang & Goldman, 2006). HDAC4 inhibits Dach2, a negative regulator of myogenin, a transcription factor that regulates denervation‐induced gene expression.…”

Section: Introductionmentioning

confidence: 99%

The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging

Walsh¹,

et al. 2015

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SummarySarcopenia, the loss of skeletal muscle mass and function during aging, is a major contributor to disability and frailty in the elderly. Previous studies found a protective effect of reduced histone deacetylase activity in models of neurogenic muscle atrophy. Because loss of muscle mass during aging is associated with loss of motor neuron innervation, we investigated the potential for the histone deacetylase (HDAC) inhibitor butyrate to modulate age‐related muscle loss. Consistent with previous studies, we found significant loss of hindlimb muscle mass in 26‐month‐old C57Bl/6 female mice fed a control diet. Butyrate treatment starting at 16 months of age wholly or partially protected against muscle atrophy in hindlimb muscles. Butyrate increased muscle fiber cross‐sectional area and prevented intramuscular fat accumulation in the old mice. In addition to the protective effect on muscle mass, butyrate reduced fat mass and improved glucose metabolism in 26‐month‐old mice as determined by a glucose tolerance test. Furthermore, butyrate increased markers of mitochondrial biogenesis in skeletal muscle and whole‐body oxygen consumption without affecting activity. The increase in mass in butyrate‐treated mice was not due to reduced ubiquitin‐mediated proteasomal degradation. However, butyrate reduced markers of oxidative stress and apoptosis and altered antioxidant enzyme activity. Our data is the first to show a beneficial effect of butyrate on muscle mass during aging and suggests HDACs contribute to age‐related muscle atrophy and may be effective targets for intervention in sarcopenia and age‐related metabolic disease.

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“…Recent studies have further probed transcriptional repression of myogenic target genes that involves recruiting HDAC complexes. So far, two well-known sequence-specific DNA-binding transcription factors, MEF2 and Six-1, have been shown to interact with different histone deacetylases HDACs (Mejat et al 2005;Tang and Goldman 2006;Cohen et al 2007), and there are conserved sites for both of these regulators in the 1-kb proximal enhancer/promoter region of myogenin that has been studied in some detail (Edmondson et al 1992;Cheng et al 1993;Yee and Rigby 1993;Spitz et al 1998). The Mef2 and Six transcription factor/corepressor/HDAC sets appear to contribute some partial repression of myogenin, and each can apparently be converted to a positive regulatory complex by replacing corepressors/HDAC activity with coactivators.…”

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confidence: 99%

A highly conserved molecular switch binds MSY-3 to regulate myogenin repression in postnatal muscle

Berghella¹,

Angelis²,

Buysscher³

et al. 2008

Genes Dev.

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Myogenin is the dominant transcriptional regulator of embryonic and fetal muscle differentiation and during maturation is profoundly down-regulated. We show that a highly conserved 17-bp DNA cis-acting sequence element located upstream of the myogenin promoter (myogHCE) is essential for postnatal repression of myogenin in transgenic animals. We present multiple lines of evidence supporting the idea that repression is mediated by the Y-box protein MSY-3. Electroporation in vivo shows that myogHCE and MSY-3 are required for postnatal repression. We further show that, in the C2C12 cell culture system, ectopic MSY-3 can repress differentiation, while reduced MSY-3 promotes premature differentiation. MSY-3 binds myogHCE simultaneously with the homeodomain protein Pbx in postnatal innervated muscle. We therefore propose a model in which the myogHCE motif operates as a switch by specifying opposing functions; one that was shown previously is regulated by MyoD and Pbx and it specifies a chromatin opening, gene-activating function at the time myoblasts begin to differentiate; the other includes MYS-3 and Pbx, and it specifies a repression function that operates during and after postnatal muscle maturation in vivo and in myoblasts before they begin to differentiate.[Keywords: CsdA; MSY-3; myogenin; Y-box; innervation; muscle maturation] Supplemental material is available at http://www.genesdev.org.

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

Cited by 82 publications

References 38 publications

Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression

Quantitative expression profiling of identified neurons reveals cell-specific constraints on highly variable levels of gene expression

The histone deacetylase inhibitor butyrate improves metabolism and reduces muscle atrophy during aging

A highly conserved molecular switch binds MSY-3 to regulate myogenin repression in postnatal muscle

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