Time- and Ventricular-Specific Expression Profiles of Genes Encoding Z-Disk Proteins in Pressure Overload Model of Left Ventricular Hypertrophy

Knyazeva, Anastasia; Krutikov, A. N.; Головкин, А. С.; Mishanin, Alexander I.; Pavlov, G. S.; Smolina, Natalia; Hushkina, Anastasia; Sejersen, Thomas; Sjöberg, Gunnar; Galagudza, M. M.; Kostareva, Anna

doi:10.3389/fgene.2018.00684

Cited by 5 publications

(4 citation statements)

References 38 publications

(38 reference statements)

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“…The Z-disk is a dense network of proteins anchoring thin filaments from opposing sarcomeres to actinins, titin, and many other structural and signaling proteins [38,39]. We observed a unique expression pattern in the genes coding for the proteins that assemble in this region, in which EDL exhibits lower expression levels compared to the psoas.…”

Section: Genes Associated With Sarcomere Z-disk Display a Unique Expr...mentioning

confidence: 86%

Comparative analysis of the transcriptomes of EDL, psoas, and soleus muscles from mice

et al. 2020

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Background Individual skeletal muscles have evolved to perform specific tasks based on their molecular composition. In general, muscle fibers are characterized as either fast-twitch or slow-twitch based on their myosin heavy chain isoform profiles. This approach made sense in the early days of muscle studies when SDS-PAGE was the primary tool for mapping fiber type. However, Next Generation Sequencing tools permit analysis of the entire muscle transcriptome in a single sample, which allows for more precise characterization of differences among fiber types, including distinguishing between different isoforms of specific proteins. We demonstrate the power of this approach by comparing the differential gene expression patterns of extensor digitorum longus (EDL), psoas, and soleus from mice using high throughput RNA sequencing. Results EDL and psoas are typically classified as fast-twitch muscles based on their myosin expression pattern, while soleus is considered a slow-twitch muscle. The majority of the transcriptomic variability aligns with the fast-twitch and slow-twitch characterization. However, psoas and EDL exhibit unique expression patterns associated with the genes coding for extracellular matrix, myofibril, transcription, translation, striated muscle adaptation, mitochondrion distribution, and metabolism. Furthermore, significant expression differences between psoas and EDL were observed in genes coding for myosin light chain, troponin, tropomyosin isoforms, and several genes encoding the constituents of the Z-disk. Conclusions The observations highlight the intricate molecular nature of skeletal muscles and demonstrate the importance of utilizing transcriptomic information as a tool for skeletal muscle characterization.

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Section: Genes Associated With Sarcomere Z-disk Display a Unique Expr...mentioning

confidence: 86%

Comparative analysis of the transcriptomes of EDL, psoas, and soleus muscles from mice

et al. 2020

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“…Interestingly, different heart compartments could also reveal distinct regional changes in Cmya5 gene expression following a disease-inducing intervention. Knyazeva et al [52] used a rodent model of pressure overload-induced heart disease and observed that Cmya5 mRNA levels declined in left ventricular samples 10 weeks following transverse aortic constriction (TAC), whereas the Cmya5 expression increased in right ventricular samples and remained unchanged in interventricular septum samples. In the same study, Fhl2 mRNA levels were not significantly altered, as it has also been shown previously in mice after TAC intervention [32].…”

Section: Discussionmentioning

confidence: 99%

CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes

et al. 2022

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Four‐and‐a‐half LIM domains protein 2 (FHL2) is an anti‐hypertrophic adaptor protein that regulates cardiac myocyte signalling and function. Herein, we identified cardiomyopathy‐associated 5 (CMYA5) as a novel FHL2 interaction partner in cardiac myocytes. In vitro pull‐down assays demonstrated interaction between FHL2 and the N‐ and C‐terminal regions of CMYA5. The interaction was verified in adult cardiac myocytes by proximity ligation assays. Immunofluorescence and confocal microscopy demonstrated co‐localisation in the same subcellular compartment. The binding interface between FHL2 and CMYA5 was mapped by peptide arrays. Exposure of neonatal rat ventricular myocytes to a CMYA5 peptide covering one of the FHL2 interaction sites led to an increase in cell area at baseline, but a blunted response to chronic phenylephrine treatment. In contrast to wild‐type hearts, loss or reduced FHL2 expression in Fhl2‐targeted knockout mouse hearts or in a humanised mouse model of hypertrophic cardiomyopathy led to redistribution of CMYA5 into the perinuclear and intercalated disc region. Taken together, our results indicate a direct interaction of the two adaptor proteins FHL2 and CMYA5 in cardiac myocytes, which might impact subcellular compartmentation of CMYA5.

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“…many Dynein Axonemal Heavy Chain proteins were repressed after ZNF354C overexpression but due to their low expression pattern in the raw RNA-Seq data, these proteins were not further studied. Also genes relevant for the cardiovascular system were suppressed by ZNF354C: Cardiomyopathy Associated 5 (CMYA5) and Actinin Alpha 2 (ACTN2) are differentially expressed in the myocardium during progression of hypertrophy 25 . Loss of murine RGS5 reduces tumour angiogenesis 20 .…”

Section: Discussionmentioning

confidence: 99%

ZNF354C is a transcriptional repressor that inhibits endothelial angiogenic sprouting

Irmer

Günther

et al. 2020

Sci Rep

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Zinc finger proteins (ZNF) are a large group of transcription factors with diverse functions. We recently discovered that endothelial cells harbour a specific mechanism to limit the action of ZNF354C, whose function in endothelial cells is unknown. Given that ZNF354C has so far only been studied in bone and tumour, its function was determined in endothelial cells. ZNF354C is expressed in vascular cells and localises to the nucleus and cytoplasm. Overexpression of ZNF354C in human endothelial cells results in a marked inhibition of endothelial sprouting. RNA-sequencing of human microvascular endothelial cells with and without overexpression of ZNF354C revealed that the protein is a potent transcriptional repressor. ZNF354C contains an active KRAB domain which mediates this suppression as shown by mutagenesis analysis. ZNF354C interacts with dsDNA, TRIM28 and histones, as observed by proximity ligation and immunoprecipitation. Moreover, chromatin immunoprecipitation revealed that the ZNF binds to specific endothelial-relevant target-gene promoters. ZNF354C suppresses these genes as shown by CRISPR/Cas knockout and RNAi. Inhibition of endothelial sprouting by ZNF354C is dependent on the amino acids DV and MLE of the KRAB domain. These results demonstrate that ZNF354C is a repressive transcription factor which acts through a KRAB domain to inhibit endothelial angiogenic sprouting.

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Time- and Ventricular-Specific Expression Profiles of Genes Encoding Z-Disk Proteins in Pressure Overload Model of Left Ventricular Hypertrophy

Cited by 5 publications

References 38 publications

Comparative analysis of the transcriptomes of EDL, psoas, and soleus muscles from mice

Comparative analysis of the transcriptomes of EDL, psoas, and soleus muscles from mice

CMYA5 is a novel interaction partner of FHL2 in cardiac myocytes

ZNF354C is a transcriptional repressor that inhibits endothelial angiogenic sprouting

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