Background – Epigenetic alterations are stable modifications to chromatin structure that occur in response to environmental cues such as hypoxia or altered nutrient delivery. DNA methylation is a well-established and dynamic DNA modification that contributes to the regulation of gene expression. In the current study, we test the hypothesize that ischemic heart failure is defined by a distinct signature of DNA methylation that corresponds with altered expression of genes involved in cardiac ventricular dysfunction. Methods and Results – Using a methylation array, we quantified genome-wide DNA methylation of endomyocardial samples acquired from patients with ischemic (n = 6) or non-ischemic (n = 5) heart failure. RNA-sequencing analysis was performed in the same samples to identify transcriptomic changes (Fold Change > 1.5, Q < 0.05, FPKM > 2) associated with differential methylation (|Percent Change| > 5%, p < 0.05). Of the promoter-associated CpG Islands, which are well-established regions of negative transcriptional regulation, we identified a signature of robust hypermethylation. The methylation changes linked to significantly decreased transcripts included key fatty acid metabolic regulators (e.g. KLF15, AGPAT9, APOA1, and MXD4). Among the few hypomethylated and induced genes was PFKFB3, which encodes for the rate-limiting enzyme of glycolysis. Gene set enrichment analysis identified TGFß as a nodal upstream regulator of the methylation changes, potentially supporting a role of DNA methylation in the increased fibrosis and apoptosis that accompanies ischemic heart failure. Conclusions – Our data identify that the DNA methylation signature recapitulates the pathologic hallmarks of ischemic heart failure. Furthermore, we show that differential DNA methylation of CpG islands within the promoter depict alterations in metabolic substrate utilization known to occur in ischemic heart failure, and may govern a return to the fetal-like metabolic program. Overall design: RNA Sequencing analysis of left ventricle samples in 11 subjects with end-stage heart failure.
Genome-wide DNA methylation encodes cardiac transcriptional reprogramming in human ischemic heart failure.
Sex, Age, Race, Subject
View SamplesLow-oxygen stress associated with natural phenomena such as waterlogging, results in widespread transcriptome changes and a metabolic switch from aerobic respiration to anaerobic fermentation. High-throughput sequencing of small RNA libraries obtained from low-oxygen stressed and control root tissue identified a total of 65 unique microRNA (miRNA) sequences from 46 families, and 14 trans-acting small interfering RNA (tasiRNA) from 3 families. Low-oxygen stress resulted in changes to the abundance of 46 miRNAs from 19 families, and all 3 tasiRNA families. Chemical inhibition of mitochondrial respiration caused similar changes in expression in a majority of the low-oxygen responsive small RNAs analysed. Our data indicate that miRNAs and tasiRNAs play a role in gene regulation and possibly developmental responses to low oxygen, and that a major signal for these responses is likely to be dependent on mitochondrial function. Keywords: Small RNA transcriptome analysis Overall design: Examination of root tissue under 2 different environments, control and low oxygen
Hypoxia-responsive microRNAs and trans-acting small interfering RNAs in Arabidopsis.
Age, Subject
View SamplesEffect on the transcriptome of an insertion in the gene At3g08610 encoding a subunit of mitochondrial complex I
Remodeled respiration in ndufs4 with low phosphorylation efficiency suppresses Arabidopsis germination and growth and alters control of metabolism at night.
Age, Specimen part, Time
View SamplesRegulation of carotenoid composition and shoot branching in Arabidopsis by a chromatin modifying histone methyltransferase, SDG8<br></br>Comparison of transcript profiles between wild type Columbia and ccr1 (carotenoid and chloroplast regulatory) mutant, which contains a mutation in At1g77300 (SDG8)
Regulation of carotenoid composition and shoot branching in Arabidopsis by a chromatin modifying histone methyltransferase, SDG8.
Age
View Samples4 week old Arabidopsis plants, of ecotype Columbia, SALK_084897 or SAIL_303_D08 were either grown under normal conditions or grown under normal conditions for before having a moderate light and drought treatment applied. Light and drought treatment was applied by withholding water for 5 days prior to transfer to 300 uE m-2 s-1 light conditions. Samples were collected after 3 days of treatment or for the same age plants grown under normal conditions.
The absence of ALTERNATIVE OXIDASE1a in Arabidopsis results in acute sensitivity to combined light and drought stress.
No sample metadata fields
View SamplesEffect of high light on directly exposed and shaded, distal Arabidopsis leaf tissue
Systemic and intracellular responses to photooxidative stress in Arabidopsis.
No sample metadata fields
View Samples4 days old seedlings grown on MS without sucrose under continuous light of sco3-1 and Col have been used to extract RNA. Microarray analysis has been performed with three independent biological replicates<br></br>
The cytoskeleton and the peroxisomal-targeted snowy cotyledon3 protein are required for chloroplast development in Arabidopsis.
Age, Time
View SamplesIn almost every countries the proportion of people over 60 years is growing faster that any other age group. Increased life expectancy is leading to the characterization of specific aspects of aging for the various physiological systems. The study of healthy aging is important to design strategies capable to maximize the health and to prevent chronic diseases in older people. Immunosenscence reflects the age-related changes of the immune system and the reduced capacity of elderly people to cope with new infections. To elucidate changes in gene expression related to systemic aging and immunosenescence in an unbiased manner we performed comparative microarray analysis on whole blood cell from healthy middle-aged versus elderly men, and correlated results with functional measurements of aerobic capacity. Blood cells from elderly subjects showed age-related changes in the expression of several markers of immunosenescence, inflammation and oxidative stress, and showed impairments in metabolic and biosynthetic capacities.
Aging: a portrait from gene expression profile in blood cells.
No sample metadata fields
View SamplesArabidopsis ATH1 Genome Arrays were used to analyse changes in transcript abundance between Col-0 (wild-type) Arabidopsis seedlings and either single T-DNA insertional KO mutants of LETM1 (At3g59820)(T-DNA lines; SALK_067558C (letm1-1) and SALK_058471 (letm1-2)) or LETM2 (At1g65540) (T-DNA line; SALK_068877 (letm2-1)). Additionally, letm1 and letm2 knock out Arabidopsis lines were crossed to generate double mutants, however a double knock-out of these two genes results in an embryo lethal phenotype. Hemizygous plants were generated that were homozygous knock out for LETM1 and heterozygous knock out for LETM2, and visa versa, termed (letm1(-/-)LETM2(+/-) and (LETM1(+/-)letm2(-/-) respectively. Note that (letm1(-/-)LETM2(+/-) displays a mild developmental defective phenotype in the first 10-14 days of growth, while (LETM1(+/-)letm2(-/-) shows no phenotype. Microarray analysis was carried out on all three single homozygous knock out lines, and also on both combinations of the hemizygous mutation between the two genes, and compared with a wild-type Col-0 control to gain insight into global transcript abundance changes in these mutant lines. Arrays were performed in triplicate for each genotype, from RNA isolated from 3 independent pools of 5-10 Arabidopsis seedlings at 10 days old.
LETM proteins play a role in the accumulation of mitochondrially encoded proteins in Arabidopsis thaliana and AtLETM2 displays parent of origin effects.
Age, Specimen part
View SamplesNull mutations in the SAL1 protein, a bi-functional protein with inositol polyphosphate-1-phosphotase activity and nucleosidase activity, result in mutants with altered leaf morphology, delayed growth and tolerance to drought stress. This experiment examines the gene expression of two SAL1 mutants, alx8 in the Col-0 background and fry1-1 in the C24 background, under normal growth conditions. In brief, RNA was extracted from the leaves of three plants of each mutant and their respective ecotypes two hours after lights on. Plants were grown under normal conditions for 5 weeks before harvesting. Each array represent a single biological replicate.
The nucleotidase/phosphatase SAL1 is a negative regulator of drought tolerance in Arabidopsis.
Age, Specimen part
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