Myogenic regulatory factors regulate M-cadherin expression by targeting its proximal promoter elements

Hsiao, Sheng Pin; Chen, Shen Liang

doi:10.1042/bj20100250

Cited by 22 publications

(26 citation statements)

References 46 publications

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“…Bhlhe40 interacts with P/CAF significantly, which reduces the interaction between P/CAF and MyoD. The same phenomenon is also seen on other MRF-targeted genes (17), suggesting the important role of Bhlhe40 in muscle differentiation. Studies from other groups also indicate that Bhlhe40 interferes with the dimerization of MyoD and E47, resulting in the downregula-tion of the myogenin, Mef2c, and myosin heavy chain (MHC) genes and prevention of myogenic differentiation (18).…”

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confidence: 57%

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Bhlhe40 Represses PGC-1α Activity on Metabolic Gene Promoters in Myogenic Cells

Chung

Kao

Villarroya

et al. 2015

Molecular and Cellular Biology

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c PGC-1␣ is a transcriptional coactivator promoting oxidative metabolism in many tissues. Its expression in skeletal muscle (SKM) is induced by hypoxia and reactive oxidative species (ROS) generated during exercise, suggesting that PGC-1␣ might mediate the cross talk between oxidative metabolism and cellular responses to hypoxia and ROS. Here we found that PGC-1␣ directly interacted with Bhlhe40, a basic helix-loop-helix (bHLH) transcriptional repressor induced by hypoxia, and protects SKM from ROS damage, and they cooccupied PGC-1␣-targeted gene promoters/enhancers, which in turn repressed PGC-1␣ transactivational activity. Bhlhe40 repressed PGC-1␣ activity through recruiting histone deacetylases (HDACs) and preventing the relief of PGC-1␣ intramolecular repression caused by its own intrinsic suppressor domain. Knockdown of Bhlhe40 mRNA increased levels of ROS, fatty acid oxidation, mitochondrial DNA, and expression of PGC-1␣ target genes. Similar effects were also observed when the Bhlhe40-mediated repression was rescued by a dominantly active form of the PGC-1␣-interacting domain (PID) from Bhlhe40. We further found that Bhlhe40-mediated repression can be largely relieved by exercise, in which its recruitment to PGC-1␣-targeted cis elements was significantly reduced. These observations suggest that Bhlhe40 is a novel regulator of PGC-1␣ activity repressing oxidative metabolism gene expression and mitochondrion biogenesis in sedentary SKM. Skeletal muscle (SKM) is one of the major metabolic organs, and it has the ability to adapt to various physiological conditions, such as cold, exercise, and sedentary life, by adjusting the balance between glycolytic and oxidative metabolism to meet the energy requirement under these conditions (1). Recent studies suggest that this adaptation relies much on the expression and activity of PGC-1␣, a transcriptional coactivator highly expressed in tissues with high energy metabolism (1, 2). PGC-1␣ enhances the activity of many nuclear receptors (NR), including peroxisome proliferator-activated receptor ␥ (PPAR␥), estrogen receptor (ER), and glucocorticoid receptor (GR), and non-NR transcription factors, such as MEF2, Sox9, FoxO1, and SREBP1 (reviewed in reference 3 and references therein), to promote oxidative metabolism, metabolic thermogenesis adaptation, biogenesis of mitochondria, gluconeogenesis, and fatty acid oxidation in various tissues (4-6). Overexpression of PGC-1␣ can promote metabolic switch from anaerobic glycolysis to oxidative metabolism (7,8). Current studies also show that PGC-1␣ plays critical roles in orchestrating the cellular response to hypoxia (9).In SKM, PGC-1␣ is preferentially expressed in oxidative metabolism-dependent slow-twitch fibers (10), and its overexpression can convert putative fast-twitch fibers into slow-twitch fibers (10). The activation of oxidative and slow-twitch muscle-specific genes by PGC-1␣ is mediated through its coactivation of Mef2 and PPAR binding to the upstream regulatory sites of these target genes (11). PGC-1␣ null mice sho...

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confidence: 57%

“…The detailed protocol for the chromatin immunoprecipitation (ChIP) assay has been described before (17). Briefly, cells and skeletal muscles were isolated and fixed in formaldehyde (1%) for 20 min.…”

Section: Plasmidsmentioning

confidence: 99%

Bhlhe40 Represses PGC-1α Activity on Metabolic Gene Promoters in Myogenic Cells

Chung

Kao

Villarroya

et al. 2015

Molecular and Cellular Biology

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“…Mef2c promoter (−3355∼+89) was amplified from mouse DNA and inserted into the EcoR I (blunted) and BamH I sites of pGL3 basic vector. The Myogenin and M-cadherin promoters have been described in our previous works [28], [29], and the MCK promoter is a generous gift from Dr. Eric Olson at University of Texas Southwestern [30].…”

Section: Methodsmentioning

confidence: 99%

Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts

Fang

Cheng

et al. 2014

PLoS ONE

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Most recent studies reported that FoxO1 transcription factor was a negative regulator of myogenesis under serum withdrawal condition, a situation not actually found in vivo. Therefore, the role of FoxO1 in myogenesis should be re-examined under more physiologically relevant conditions. Here we found that FoxO1 was preferentially localized to nucleus in proliferating (PMB) and confluent myoblasts (CMB) and its nuclear exclusion was a prerequisite for formation of multinucleated myotubes (MT). The nuclear shuttling of FoxO1 in PMB could be prevented by leptomycin B and we further found that cytoplasmic accumulation of FoxO1 in myotubes was caused by the blockade of its nuclear import. Although over-expression of wildtype FoxO1 in C2C12 myoblasts significantly blocked their myogenic differentiation under serum withdrawal condition, application of insulin and LiCl, an activator of Wnt signaling pathway, to these cells successfully rescued their myogenic differentiation and generated myotubes with larger diameters. Interestingly, insulin treatment significantly reduced FoxO1 level and also delayed nuclear re-accumulation of FoxO1 triggered by mitogen deprivation. We further found that FoxO1 directly repressed the promoter activity of myogenic genes and this repression can be relieved by insulin and LiCl treatment. These results suggest that FoxO1 inhibits myogenesis in serum withdrawal condition but turns into a hypertrophy potentiator when other myogenic signals, such as Wnt and insulin, are available.

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“…A quantitative real-time RT-PCR experiment was subsequently used to obtain more-accurate data [36]. Two sets of primers, GSP4/GSP5 and GSP6/GSP7, were respectively used to amplify the cDNA fragments of GRS1 and GRS2 .…”

Section: Methodsmentioning

confidence: 99%

Saccharomyces cerevisiae Possesses a Stress-Inducible Glycyl-tRNA Synthetase Gene

Chen¹,

Wu²,

Huang³

et al. 2012

PLoS ONE

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Aminoacyl-tRNA synthetases are a large family of housekeeping enzymes that are pivotal in protein translation and other vital cellular processes. Saccharomyces cerevisiae possesses two distinct nuclear glycyl-tRNA synthetase (GlyRS) genes, GRS1 and GRS2 . GRS1 encodes both cytoplasmic and mitochondrial activities, while GRS2 is essentially silent and dispensable under normal conditions. We herein present evidence that expression of GRS2 was drastically induced upon heat shock, ethanol or hydrogen peroxide addition, and high pH, while expression of GRS1 was somewhat repressed under those conditions. In addition, GlyRS2 (the enzyme encoded by GRS2 ) had a higher protein stability and a lower K M value for yeast tRNA Gly under heat shock conditions than under normal conditions. Moreover, GRS2 rescued the growth defect of a GRS1 knockout strain when highly expressed by a strong promoter at 37°C, but not at the optimal temperature of 30°C. These results suggest that GRS2 is actually an inducible gene that may function to rescue the activity of GRS1 under stress conditions.

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Myogenic regulatory factors regulate M-cadherin expression by targeting its proximal promoter elements

Cited by 22 publications

References 46 publications

Bhlhe40 Represses PGC-1α Activity on Metabolic Gene Promoters in Myogenic Cells

Bhlhe40 Represses PGC-1α Activity on Metabolic Gene Promoters in Myogenic Cells

Insulin and LiCl Synergistically Rescue Myogenic Differentiation of FoxO1 Over-Expressed Myoblasts

Saccharomyces cerevisiae Possesses a Stress-Inducible Glycyl-tRNA Synthetase Gene

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