Alkaline nucleoplasm facilitates contractile gene expression in the mammalian heart
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ABSTRACT:
PROVIDER: PRJNA804899 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17960937_1.fastq.gz | Fastqsanger.gz | |||
| SRR17960937_2.fastq.gz | Fastqsanger.gz | |||
| SRR17960938_1.fastq.gz | Fastqsanger.gz | |||
| SRR17960938_2.fastq.gz | Fastqsanger.gz | |||
| SRR17960939_1.fastq.gz | Fastqsanger.gz |
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Project description:Alkaline nucleoplasm facilitates contractile gene expression in the mammalian heart [ChIP-seq]
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Project description:Alkaline nucleoplasm facilitates contractile gene expression in the mammalian heart [RNA-seq]
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Project description:Cardiac contractile strength is recognised as highly pH-sensitive, but less is known about the influence of pH on cardiac gene expression, which may be relevant during changes in myocardial metabolism or vascularization in development or disease. We sought evidence for pH-responsive cardiac genes and a context in which this has physiological relevance. pHLIP, a peptide-based reporter of acidity, revealed a non-uniform pH landscape in early-postnatal myocardium, dissipating in later life. pH-responsive differentially-expressed genes (pH-DEGs) were identified by transcriptomics of neonatal cardiomyocytes cultured over a range of pH. Enrichment analysis indicated “striated muscle contraction” as a pH-responsive biological process. Label-free proteomics verified fifty-four pH-responsive gene-products, including contractile elements and the adaptor protein CRIP2. Using transcriptional assays, acidity was found to inhibit p300/CBP acetylase activity and, as its functional readout, negatively affect myocardin, a co-activator of cardiac gene expression. In cultured myocytes, acid-inhibition of p300/CBP reduced H3K27 acetylation, as demonstrated by chromatin immunoprecipitation. H3K27ac levels were more strongly reduced at promoters of acid-downregulated DEGs, suggesting an epigenetic mechanism of pH-sensitive gene expression. By tandem cytoplasmic/nuclear pH imaging, the cardiac nucleus was found to exercise a degree of control over its pH through Na+/H+ exchangers at the nuclear envelope. Thus, we describe how extracellular pH signals gain access to the nucleus and regulate the expression of a subset of cardiac genes, notably those coding for contractile proteins and Crip2. Acting as a proxy of a well-perfused myocardium, alkaline conditions are permissive for expressing genes related to the contractile apparatus.
2022-04-06 | GSE196438 | GEO
Project description:Cardiac contractile strength is recognised as highly pH-sensitive, but less is known about the influence of pH on cardiac gene expression, which may be relevant during changes in myocardial metabolism or vascularization in development or disease. We sought evidence for pH-responsive cardiac genes and a context in which this has physiological relevance. pHLIP, a peptide-based reporter of acidity, revealed a non-uniform pH landscape in early-postnatal myocardium, dissipating in later life. pH-responsive differentially-expressed genes (pH-DEGs) were identified by transcriptomics of neonatal cardiomyocytes cultured over a range of pH. Enrichment analysis indicated “striated muscle contraction” as a pH-responsive biological process. Label-free proteomics verified fifty-four pH-responsive gene-products, including contractile elements and the adaptor protein CRIP2. Using transcriptional assays, acidity was found to inhibit p300/CBP acetylase activity and, as its functional readout, negatively affect myocardin, a co-activator of cardiac gene expression. In cultured myocytes, acid-inhibition of p300/CBP reduced H3K27 acetylation, as demonstrated by chromatin immunoprecipitation. H3K27ac levels were more strongly reduced at promoters of acid-downregulated DEGs, suggesting an epigenetic mechanism of pH-sensitive gene expression. By tandem cytoplasmic/nuclear pH imaging, the cardiac nucleus was found to exercise a degree of control over its pH through Na+/H+ exchangers at the nuclear envelope. Thus, we describe how extracellular pH signals gain access to the nucleus and regulate the expression of a subset of cardiac genes, notably those coding for contractile proteins and Crip2. Acting as a proxy of a well-perfused myocardium, alkaline conditions are permissive for expressing genes related to the contractile apparatus.
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2022-04-06 | GSE196439 | GEO
Project description:Lotus japonicus is a model legume broadly used to study transcriptome regulation under different stress conditions and microorganism interaction. Understanding how this model plant respond gainst alkaline stress will certainly help to develop more tolerant cultivars in economically important Lotus species as well as in other legumes. In order to uncover the most important response mechanisms activated during alkaline stress, we explored by microarray analysis the transcriptome regulation occurring in the phenotypically contrasting ecotypes MG-20 and Gifu B-129 of L. japonicus after 21 days of alkaline stress.
2014-03-25 | E-MTAB-2418 | biostudies-arrayexpress
Project description:Impaired myocardial contractile function is a hallmark of heart failure (HF) which may present under resting conditions and/or during physiological stress. Previous studies reported that high fat feeding in HF is associated with improved myocardial contractile function at baseline. Our goal was to determine whether myocardial function is compromised in response to physiological stress and to evaluate the global gene expression profile of rats fed high dietary fat following infarction. Male Wistar rats underwent ligation or sham surgery and were fed normal (10% kcal fat) (SHAM+NC, HF+NC) or high fat (60% kcal saturated fat) (SHAM+SAT, HF+SAT) for 8 weeks. Myocardial contractile function was assessed using a Millar pressure-volume (PV) conductance catheter at baseline, during inferior vena caval occlusions and dobutamine (DOB) stress. Steady state indices of systolic function, left ventricular (LV)+dP/dtmax, stroke work and maximal power were increased in HF+SAT vs HF+NC; HF+NC were reduced vs SHAM+NC. Preload-recruitable measures of contractility [end systolic PV relationship, maximal elastance, preload recruitable SW and peak+dP/dtmax to end diastolic volume] were decreased in HF+NC but not HF+SAT. β-adrenergic responsiveness (delta-LV+dP/dtmax and delta-cardiac output DOB 0-10 µg•kg-1•min-1) was reduced in HF, but high fat feeding did not further impact contractile reserve in HF. Contractile reserve was reduced by high fat in SHAM+SAT. Microarray gene expression analysis reveals the majority of significantly altered pathways identified to contain multiple gene targets correspond to cell signaling pathways and energy metabolism. These findings suggest that high saturated fat improves myocardial function at rest and during physiological stress in infarcted hearts, but may negatively impact contractile reserve under non-pathological conditions. Furthermore, high fat feeding-induced alterations in gene expression related to energy metabolism and specific signaling pathways reveal promising targets through which high saturated fat potentially mediates cardioprotection in heart failure/LV dysfunction. Comparison of gene expression in heart failure or sham surgery hearts exposed to saturated or normal diets. Male Wistar rats (300-350g) were maintained on a reverse light-dark cycle and all procedures were done 3-6 hours into the dark phase cycle to synchronize with the normal active state of the rodents. Rats were randomly assigned to receive either a sham-operation (SH) or coronary ligation to induce cardiac dysfunction (HF). Heart failure was induced by ligating the left main coronary artery. Following surgery, rats were immediately fed either a normal rodent chow (NC) or a high saturated fat chow (SAT) with 60% caloric content derived from fat (25% palmitic, 33% stearic, 33% oleic acid, Research Diets).
2010-09-01 | E-GEOD-21021 | biostudies-arrayexpress
Project description:To investigate the rapid adaptation mechanism of Bacillus thuringiensis in an alkaline environment, we have employed whole genome microarray expression profiling as a discovery platform to identify the difference of gene expression between normal condition and alkaline condition.
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Project description:RPL3L-containing ribosomes modulate mitochondrial activity in the mammalian heart.
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