Werner syndrome (WS) is a human adult progeroid syndrome caused by loss-of-function mutations in the WRN RECQ helicase gene. We analyzed mRNA and miRNA expression in fibroblasts from WS patients and in fibroblasts depleted of WRN protein in order to determine the role of WRN in transcription regulation, and to identify genes and miRNAs that might drive WS disease pathogenesis. Genes altered in WS cells participate in cellular growth, proliferation and survival; in tRNA charging and in oncogenic signaling; and in connective tissue and developmental networks. Genes down-regulated in WS cells were highly enriched in Gquadruplex (G4) DNA motifs, indicating G4 motifs are physiologic substrates for WRN. In contrast, there was a remarkable, coordinate up-regulation of nearly all of the cytoplasmic tRNA synthetases and of genes associated with the senescence-associated secretory phenotype (SASP). These results identify canonical pathways that may drive the pathogenesis of Werner syndrome and associated disease risks.
The Werner syndrome RECQ helicase targets G4 DNA in human cells to modulate transcription.
Sex, Age, Specimen part, Cell line
View SamplesThe aim of this experiment is to test the ability of the ortholog of Arabidopsis LFY gene from Leanworthia crassa (Lcr) to complement an Arabidopsis LFY mutant. Plants used are homozygous lfy6 mutants (EMS alleles) in Ler background which are transformed or not (for the lfy6 mutant) by genomic clones for Arabidopsis LFY (AthLFY) or Leanworthia crassa LFY (LcrLFY). Flowering was synchronized by growing plants in SD then shifting them to LD. 2 time points samples (wild type Ler) were taken at the end of the SD period as a reference for genes induced by shifting to LD, irrespective of the status at the LFY locus.
Evolutionary divergence of LFY function in the mustards Arabidopsis thaliana and Leavenworthia crassa.
Age, Specimen part, Time
View SamplesBloom syndrome is a rare autosomal recessive genetic instability and cancer predisposition syndrome caused by loss of function mutations in the BLM RECQ helicase gene. To ask if some of the distinctive pathological features of Bloom syndrome might reflect altered gene expression, we analyzed global mRNA and miRNA expression in fibroblasts from 16 patients and 15 matched normal controls, and in control primary diploid fibroblasts depleted of the BLM protein. We document significant differential expression of both protein-coding genes and miRNAs with well-characterized cancer associations in BLM-deficient cells. Differences in expression correlated significantly with G4 motifs, which are associated with potential to form G-quadruplex structures. These results indicate that BLM helicase may modulate gene expression by regulating the in vivo stability of G-quadruplex structures, and identify sets of genes and miRNAs whose expression, when altered, may drive the pathogenesis of Bloom syndrome and associated cancers.
Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs.
Sex, Age, Specimen part, Cell line
View SamplesOnconase represents a new class of RNA-damaging drugs. Mechanistically, Onconase is thought to internalize, where it degrades intracellular RNAs such as tRNA and double-stranded RNA, and thereby suppresses protein synthesis. However, there may be additional or alternative mechanism(s) of action.
Onconase responsive genes in human mesothelioma cells: implications for an RNA damaging therapeutic agent.
Specimen part, Cell line
View SamplesWe assessed the gene expression profile of purified CD205+CD8+ Dendritic Cells isolated from murine spleens.
NOD2 modulates immune tolerance via the GM-CSF-dependent generation of CD103<sup>+</sup> dendritic cells.
Sex, Age, Specimen part
View SamplesGene expression profiles from 280 formalin-fixed and paraffin embedded normal and tumor samples of four cancer types
Regulatory T-cell Genes Drive Altered Immune Microenvironment in Adult Solid Cancers and Allow for Immune Contextual Patient Subtyping.
Sex, Age, Specimen part
View SamplesMM1S cells have been cultured under normoxic and hypoxic conditions, and gene expression profiling has been performed using the Affymetrix Human Genome U133 Plus 2.0 array.
Metabolic signature identifies novel targets for drug resistance in multiple myeloma.
Cell line
View SamplesThe tumoral clone of Waldenstrms macroglobulinemia (WM) shows a wide morphological heterogeneity which ranges from B-lymphocytes (BL) to plasma cells (PC). By means of genome-wide expression profiling we have been able to identify genes exclusively deregulated in BL and PC from WM, but with a similar expression pattern in their corresponding cell-counterparts from CLL and MM, as well as normal individuals. The differentially expressed genes have important functions in B-cell differentiation and oncogenesis. Thus, two of the genes down-regulated in WM-BL were IL4R, which plays a relevant role in CLL B cell survival, and BACH2 that participates in the development of class-switched PC. Interestingly, one of the up-regulated genes in WM-BL was IL6. A set of 4 genes was able to discriminate clonal B-lymphocytes from WM and CLL: LEF1 (WNT/catenin pathway), MARCKS, ATXN1 and FMOD. We also found deregulation of genes involved in plasma cell differentiation such as PAX5 which was overexpressed in WM-PC, and IRF4 and BLIMP1 which were underexpressed. In addition, three of the target genes activated by PAX5 -CD79, BLNK and SYK- were up-regulated in WM-PC. In summary, these results indicate that both PC and BL from WM are genetically different from the MM and CLL cell-counterpart.
Gene expression profiling of B lymphocytes and plasma cells from Waldenström's macroglobulinemia: comparison with expression patterns of the same cell counterparts from chronic lymphocytic leukemia, multiple myeloma and normal individuals.
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View SamplesNucleosomal incorporation of specialized histone variants is an important mechanism to generate different functional chromatin states. Here we report the identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y. Their mRNAs are found in certain human cell lines, in addition to several normal and malignant human tissues. In keeping with their primate-specificity, H3.X and H3.Y are detected in different brain regions. Transgenic H3.X and H3.Y proteins are stably incorporated into chromatin in a similar fashion to the known H3 variants. Importantly, we demonstrate biochemically and by mass spectrometry that endogenous posttranslationally modified H3.Y protein exists in vivo, and that stress-stimuli, such as starvation and cellular density, increase the abundance of H3.Y-expressing cells. Global transcriptome analysis revealed that knock-down of H3.Y affects cell growth and leads to changes in the expression of many genes involved in cell cycle control. Thus, H3.Y is a novel histone variant involved in the regulation of cellular responses to outside stimuli.
Identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways.
Age, Specimen part
View Samples