Autophagy as a conserved degradation and recycling machinery is important in normal development and physiology, and defects in this process are linked to many kinds of disease. Because too much or too little autophagy can be detrimental, the process must be tightly regulated both temporally and in magnitude. The transcriptional induction and repression of the autophagy-related (ATG) genes is one crucial aspect of this regulation, but the transcriptional regulators that modulate autophagy are not well characterized. In this study, we identified Pho23 as a master transcriptional repressor for autophagy, with transcriptome profiling revealing that ATG9 is one of the key target genes. Physiological studies with a PHO23 null mutant, or with strains expressing modulated levels of Atg9, demonstrate a critical role of this protein as a regulator of autophagosome formation frequency; Atg9 protein levels correlate with the number of autophagosomes generated upon autophagy induction, and the level of autophagy activity. Overall design: WT yeast and pho23 deletion mutants were grown under nutrient rich or nitrogen starvation conditions; gene expression was quantified across these 4 samples.
Transcriptional regulation by Pho23 modulates the frequency of autophagosome formation.
Subject
View SamplesPurpose: ATG41 is involved both in autophagy and zinc-deficient growth. The goal of this study is to compare transcriptomic profiles of wild-type and atg41? strains to discover autophagy-independent molecular phenotypes for the mutant. The atg1? mutant is a control for autophagy activity. Methods: Wild-type and mutant yeast were grown to mid-log phase in replete medium and shifted to zinc-deficient medium for 8 hours, after which, cells were harvested for RNA sequencing to detect differential gene expression. Results: Gene expression data for virtually every gene (~6,000) was obtained with ~12,000,000 reads per sample. Differential gene expression analysis showed that several hundred genes were differentially experessed in the atg41? mutant (greater than 2-fold) at an FDR of 0.5. Conclusions: Most strikingly, we found that the atg41? mutant transcriptome shows signs that sulfur metabolism is distrupted during zinc-deficinet growth. Expression of Met4 gene targets is increased. Overall design: mRNA from wild-type, atg1?, and atg41? yeast strains was prepared from zinc-deficient cultures in quadruplicate and sequenced. Single-end, 100bp sequencing was performed, using v4 SBS chemistry on an Illumina HiSeq2500 sequencer.
An Autophagy-Independent Role for <i>ATG41</i> in Sulfur Metabolism During Zinc Deficiency.
Cell line, Subject
View SamplesGlucocorticoids are first-line agents for the treatment of many eosinophil-associated disorders. However, their mechanism of action in this group of disorders remains poorly understood, including the well-known clinical observation that glucocorticoids at therapeutic doses lead to profound, transient eosinopenia within hours of administration. To gain an unbiased, genome-wide view of the early transcriptional effects of glucocorticoids on human eosinophils in vivo, and torelate them to the kinetics of glucocorticoid-induced eosinopenia, RNA sequencing was performed on purified blood eosinophils obtained before and 30, 60, and 120 minutes after administration of a single dose of oral prednisone (1 mg/kg) to healthy subjects with hypereosinophilia (hypereosinophilia of unknown significance). Overall design: Three subjects with hypereosinophilia of unknown significance were each given a single dose of oral prednisone, 1 mg/kg. Whole blood was collected before and 30 minutes, 1 hour, and 2 hours after prednisone administration. Eosinophils were purified from each peripheral blood sample. Total RNA was obtained from purified eosinophils and subject to library preparation and high-throughput sequencing.
Transcript- and protein-level analyses of the response of human eosinophils to glucocorticoids.
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View SamplesPatients with Klinefelter Syndrome have the karyotype 47,XXY. These men are suffering from hypergonadotropic hypogonadism and are infertile. It is debated whether the different hormonal constitution observed in these patients or different gene expression
Gene expression patterns in relation to the clinical phenotype in Klinefelter syndrome.
Sex, Specimen part
View SamplesExpression data from CD34+ hematopoietic cells transduced with control or anti-SLPI shRNA, serum starved and treated with G-CSF.
A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in granulocytic differentiation.
Specimen part
View SamplesGene expression patterns of testicular seminoma were analysed applying oligonucleotide microarrays in 40 specimens of different tumour stages (pT1, pT2, pT3) and in 3 normal testes.
Gene signatures of testicular seminoma with emphasis on expression of ets variant gene 4.
No sample metadata fields
View SamplesConrad et al. Nature 456, 344349 (2008) have generated human adult germline stem cells (haGSCs) from human testicular tissue, which they claim have similar pluripotent properties to human embryonic stem cells (hESCs). Here we investigate the pluripotency of haGSCs by using global gene-expression analysis based on their gene array data and comparing the expression of pluripotency marker genes in haGSCs and hESCs, and in haGSCs and human fibroblast samples derived from different laboratories, including our own. We find that haGSCs and fibroblasts have a similar gene-expression profile, but that haGSCs and hESCs do not. The pluripotency of Conrad and colleagues haGSCs is therefore called into question.
Human adult germline stem cells in question.
Specimen part
View SamplesKnockdown of HCLS1 mRNA in CD34+ hematopoietic cells resulted in a severe diminished in vitro myeloid differentiation which was in line with downregulation of a set of genes, e.g., of Wnt or PI3K/Akt signaling cascades. We performed microarrays to evaluate specific genes and signaling systems regulated by HCLS1 in hematopoietic cells.
Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis.
Specimen part, Disease, Disease stage, Treatment
View SamplesRats were given pulmonary embolism by i.v. injection of 25 micron polystyrene microspheres or 0.01% Tween20 solution as vehicle control
Differential effect of mild and severe pulmonary embolism on the rat lung transcriptome.
No sample metadata fields
View SamplesBP and ER encode proteins that act synergistically to regulate Arabidopsis inflorescence architecture. To search for genes/proteins that influence the BP/ER signaling pathways, we conducted mutagenesis of the bp er double mutant and found that a mutation in FILAMENTOUS FLOWER (FIL) suppresses many of the morphological/developmental defects in bp er. Given that FIL encodes a Zn-finger containing transcription factor, microarray analysis was conducted on bp er vs. the bp er fil line to identify genes that are misregulated and which might implicate specific genes/proteins/pathways that are involved in regulating inflorescence development.
A novel Filamentous Flower mutant suppresses brevipedicellus developmental defects and modulates glucosinolate and auxin levels.
No sample metadata fields
View Samples