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Effect of ATF4 overexpression on mRNA levels in differentiated C2C12 myotubes.

ABSTRACT: ATF4 is a bZIP transcription factor that that promotes skeletal muscle atrophy. The goal of these studies was to determine the effects of ATF4 overexpression on mRNA levels in differentiated C2C12 myotubes. For additional details see Ebert et al, Stress-Induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy. JBC epub. June 12,2012

ORGANISM(S): Mus musculus

PROVIDER: GSE39194 | GEO | 2012/09/15

SECONDARY ACCESSION(S): PRJNA170207

REPOSITORIES: GEO

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Effect of ATF4 gene knockout on skeletal muscle mRNA levels in fasted mice.

2012-09-15 | GSE39193 | GEO

Effect of Gadd45a overexpression on mouse skeletal muscle mRNA levels.

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Effect of ATF4 gene knockout on skeletal muscle mRNA levels in fasted mice.

Project description:ATF4 is a fasting-induced trascription factor that promotes skeletal muscle atrophy. The goal of these studies was to determine how of loss of ATF4 affects skeletal muscle mRNA expression. For additional details see Ebert et al, Stress-Induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy. JBC epub. June 12, 2012. Muscle-specfic ATF4 knockout (ATF4 mKO) mice and littermate controls were fasted for 24 hours and then tibialis anterior muscles were harvested. mRNA levels in ATF4 mKO muscles were normalized to levels in littermate control muscles.

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Effect of ATF4 overexpression on mRNA levels in differentiated C2C12 myotubes.

Project description:ATF4 is a bZIP transcription factor that that promotes skeletal muscle atrophy. The goal of these studies was to determine the effects of ATF4 overexpression on mRNA levels in differentiated C2C12 myotubes. For additional details see Ebert et al, Stress-Induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy. JBC epub. June 12,2012 C2C12 myotubes were infected with adenovirus co-expressing eGFP and ATF4-FLAG. Control myotubes were infected with adenovirus co-expressing eGFP and a transcriptionally inactive ATF4 construct (ATF4∆bZIP).

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Effect of Gadd45a overexpression on mouse skeletal muscle mRNA levels.

Project description:Gadd45a is a stress-induced protein that causes skeletal muscle atrophy. The goal of these studies was to determine the effects of Gadd45a overexpression on mRNA levels in mouse skeletal muscle. For additional details see Ebert et al, Stress-Induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy. JBC epub. June 12, 2012. Tibialis anterior (TA) muscles from muscle-specfic ATF4 knockout mice (ATF4 mKO) were transfected with either 20 mg empty plasmid (pcDNA3) (left TA) or 20 mg pCMV-FLAG-Gadd45a (right TA) and harvested 7 days later. mRNA levels in Gadd45a-transfected muscles were normalized to levels in control transfected muscles.

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Project description:Muscle denervation causes skeletal muscle atrophy. The goal of these studies was to determine the effects of denervation on skeletal muscle mRNA levels in C57BL/6 mice. For additional details see Ebert et al, Stress-Induced Skeletal Muscle Gadd45a Expression Reprograms Myonuclei and Causes Muscle Atrophy. JBC epub. June 12, 2012. Left sciatic nerves of C57BL/6 mice were transected. Seven days later bilateral tibialis anterior muscles were harvested. mRNA levels in denervated muscles were normalized to levels in contralateral innervated muscles.

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ATF4 Promotes Skeletal Muscle Atrophy by Forming a Heterodimer with C/EBPbeta

Project description:Skeletal muscle atrophy is a highly prevalent and debilitating condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves activating transcription factor 4 (ATF4), a protein in the basic leucine zipper (bZIP) transcription factor family. However, the direct biochemical mechanism by which ATF4 promotes muscle atrophy was unknown. Because bZIP proteins such as ATF4 must dimerize to bind and activate genes, and because ATF4 is unable to form highly stable homodimers, we hypothesized that ATF4 may promote muscle atrophy by heterodimerizing with another bZIP family member. To test this hypothesis, we biochemically isolated skeletal muscle proteins that associate with the dimerization- and DNA-binding domain of ATF4 (the bZIP domain) in mouse skeletal muscle fibers in vivo. Interestingly, we found that ATF4 makes up one half of at least 5 distinct heterodimeric bZIP transcription factors in skeletal muscle fibers. This three-way interaction between ATF4, C/EBPbeta and the ATF4-C/EBP composite site activates the Gadd45a gene, which encodes a known mediator of muscle atrophy (Gadd45a). Together, these results identify a direct biochemical mechanism by which ATF4 induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level.

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Effect of muscle-specific ATF4 gene knockout (ATF4 mKO) on skeletal muscle mRNA levels in aged mice.

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Effect of muscle-specific ATF4 gene knockout (ATF4 mKO) on skeletal muscle mRNA levels in aged mice.

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2015-09-03 | GSE72658 | GEO

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