Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts

Zhang, Xiaomin; Azhar, Gohar; Helms, Scott; Burton, Brian; Huang, Chris; Zhang, Ying; Gu, Xuesong; Fang, Hong; Tong, Weida; Wei, Jeanne Y.

doi:10.4137/grsb.s7457

Cited by 9 publications

(14 citation statements)

References 84 publications

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“…In our luciferase assays, constitutively active GPR56 stimulated NFAT transcription to a lesser degree than SRE transcription. One of the target genes of the SRF is FHL1 [53, 45], a co-activator of NFAT transcription in the muscle [48]. Increased FHL1 expression was seen in GPR56 knockout myoblasts, but not in GPR56 silenced C2C12 cells.…”

Section: Discussionmentioning

confidence: 99%

“…3D). Decreases in signalling to the SRF transcription factor could result in reduced expression of the downstream transcription factors MyoD and myogenin, which regulate differentiation [43][44][45]. Indeed, MyoD expression appeared to be decreased at days 3 and 5 in the differentiating knockout compared to wild-type myoblasts at similar time points, whereas there was no change in the early marker of differentiation, myogenin.…”

Section: Primary Myoblasts From Gpr56-knockout Mice Exhibit Decreasedmentioning

confidence: 99%

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G‐protein coupled receptor 56 promotes myoblast fusion through serum response factor‐ and nuclear factor of activated T‐cell‐mediated signalling but is not essential for muscle development in vivo

Doyle

Barry

et al. 2013

The FEBS Journal

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Mammalian muscle cell differentiation is a complex process of multiple steps for which many of the factors involved have not yet been defined. In a screen to identify the regulators of myogenic cell fusion, we found that the G-protein coupled receptor 56 (GPR56) gene was transiently upregulated during the early fusion of human myoblasts. Human mutations in GPR56 cause the disease bilateral frontoparietal polymicrogyria (BFPP), however the consequences of receptor dysfunction on muscle development have not been explored. Using knockout mice, we defined the role of GPR56 in skeletal muscle. GPR56−/− myoblasts have decreased fusion and smaller myotube sizes in culture. In addition, loss of GPR56 expression in muscle cells results in decreases or delays in the expression of MyoD, myogenin, and NFATc2. Our data suggest that these abnormalities result from decreased GPR56-mediated SRE and NFAT signaling. Despite these changes, no overt differences in phenotype were identified in the muscle of GPR56 knockout mice, which presented only a mild but statistically significant elevation of serum creatine kinase (CK) compared to wildtype. In agreement with these findings, clinical data from 13 BFPP patients revealed mild serum CK increase in only 2 patients. In summary, targeted disruption of GPR56 in mice results in myoblast abnormalities. The absence of a severe muscle phenotype in GPR56 knockout mice and human patients suggests that other factors may compensate for the lack of this GPCR during muscle development and that the motor delay observed in these patients is likely not due to primary muscle abnormalities.

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Section: Discussionmentioning

confidence: 99%

Section: Primary Myoblasts From Gpr56-knockout Mice Exhibit Decreasedmentioning

confidence: 99%

G‐protein coupled receptor 56 promotes myoblast fusion through serum response factor‐ and nuclear factor of activated T‐cell‐mediated signalling but is not essential for muscle development in vivo

Doyle

Barry

et al. 2013

The FEBS Journal

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“…SRF is an important cardiac transcription factor necessary for the regulation of genes involved in cardiac structure and function [20] but also in metabolism, ion transport, and stress responses [21]. In fibroblasts the SRF gene is rapidly but only transiently induced in response to serum stimulation [22] Thus, SRF levels reach their peak at approximately 2 hours and return to basal levels 6 hours after serum stimulation.…”

Section: Discussionmentioning

confidence: 99%

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

Lutze¹,

Wanka²,

Bäumgen³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Renin is known as a secretory glycoprotein that ultimately leads to angiotensin II generation. In this way renin exerts pro-inflammatory effects and promotes cardiac injury. Additional transcripts have been identified encoding for a cytosolic renin isoform that - in contrast to secretory renin - exhibits cardioprotective effects under ischemic conditions. The promoter of these transcripts is unknown. Methods: Using qRT-PCR and dual-luciferase reporter assay we examined the expression and promotor activity of cytosolic renin as well as the regulation by glucose starvation in H9c2 cardiomyoblasts. Results: We identified a promoter in intron1 of the rat renin gene with two glucose starvation-sensitive regions. One region contains a binding motif for serum response factor (SRF). Under glucose depletion expression of SRF increased prior to cytosolic renin. SRF knock down selectively decreased cytosolic renin expression and attenuated the increase of cytosolic renin expression under glucose depletion. Conclusions: Transcripts encoding for secretory and cytosolic renin are differentially expressed. The low basal expression of cytosolic renin as well as its induction under ischemia-related conditions represents an efficient system regulated in accordance with its previously identified unfavorable effects under control situations but protective effects seen after myocardial infarction or glucose depletion.

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“…This ubiquitously expressed TF binds DNA as a dimer (through the highly conserved DNA-binding and dimerization MADS-box domain) and regulates many target genes through serum response elements in their promoters (reviewed in [58,59]). More than 200 SRF-dependent genes that are important for metabolism, cytoskeleton, extracellular matrix, ion transport, stress response, transcription, and translational regulation have been identified in the ventricular myocardium [24,60]. Alternative splicing generates several isoforms of SRF, with full-length SRF being the predominant cardiac isoform.…”

Section: Srf and Myocardin Transcriptional Regulatorsmentioning

confidence: 99%

Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease

Михайлов

Torrado

2016

Heart Fail Rev

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There are multiple intrinsic mechanisms for diastolic dysfunction ranging from molecular to structural derangements in ventricular myocardium. The molecular mechanisms regulating the progression from normal diastolic function to severe dysfunction still remain poorly understood. Recent studies suggest a potentially important role of core cardio-enriched transcription factors (TFs) in the control of cardiac diastolic function in health and disease through their ability to regulate the expression of target genes involved in the process of adaptive and maladaptive cardiac remodeling. The current relevant findings on the role of a variety of such TFs (TBX5, GATA-4/6, SRF, MYOCD, NRF2, and PITX2) in cardiac diastolic dysfunction and failure are updated, emphasizing their potential as promising targets for novel treatment strategies. In turn, the new animal models described here will be key tools in determining the underlying molecular mechanisms of disease. Since diastolic dysfunction is regulated by various TFs, which are also involved in cross talk with each other, there is a need for more in-depth research from a biomedical perspective in order to establish efficient therapeutic strategies.

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Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts

Cited by 9 publications

References 84 publications

G‐protein coupled receptor 56 promotes myoblast fusion through serum response factor‐ and nuclear factor of activated T‐cell‐mediated signalling but is not essential for muscle development in vivo

G‐protein coupled receptor 56 promotes myoblast fusion through serum response factor‐ and nuclear factor of activated T‐cell‐mediated signalling but is not essential for muscle development in vivo

An Alternative Promoter in Intron1 of the Renin Gene is Regulated by Glucose Starvation via Serum Response Factor

Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease

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