Here we uncover antagonistic regulation of transcript levels in the germline of Caenorhabditis elegans hermaphrodites. The histone methyltransferase MES-4 marks genes expressed in the germline with methylated Lys36 on histone H3 (H3K36me) and promotes their transcription; MES-4 also represses genes normally expressed in somatic cells and genes on the X chromosomes. The DRM complex, which includes E2F/DP and Retinoblastoma homologs, affects germline gene expression and prevents excessive repression of X-chromosome genes. Using genome-scale analyses of germline tissue, we show that common germline-expressed genes are activated by MES-4 and repressed by DRM, and that MES-4 and DRM co-bind many germline-expressed genes. Reciprocally, MES-4 represses and DRM activates a set of autosomal soma-expressed genes and overall X-chromosome gene expression. Mutations in mes-4 or the DRM subunit lin-54 oppositely skew target transcript levels and cause sterility; a double mutant restores near wild-type transcript levels and germ cell development. Together, yin-yang regulation by MES-4 and DRM ensures transcript levels appropriate for germ cell function, elicits robust but not excessive dampening of X-chromosome-wide transcription, and may poise genes for future expression changes. Our study reveals that conserved transcriptional regulators implicated in development and cancer counteract each other to fine-tune transcript dosage.
Opposing activities of DRM and MES-4 tune gene expression and X-chromosome repression in Caenorhabditis elegans germ cells.
Sex
View SamplesHyperthermia (HT) treatments in combination with either chemotherapy, radiotherapy or both are used for patients with cancer in various organs. However, the acquisition of thermotolerance in cancer cells due to the increase in cytoprotective proteins attenuates the therapeutic effects of HT. BAG3 (BCL2-associated athanogene 3) is a cytoprotective protein that acts against various stresses including heat stress. Recently, we demonstrated that the inhibition of BAG3 improves cell death sensitivity to HT in cancer cells. However, a detailed molecular mechanism involved in the enhancement of HT sensitivity by BAG3-knockdown (KD) in cancer cells is unclear.
Network analysis of genes involved in the enhancement of hyperthermia sensitivity by the knockdown of BAG3 in human oral squamous cell carcinoma cells.
Sex, Age, Specimen part, Cell line
View SamplesHyperthermia (HT) is widely used to treat patients with various cancers. In general, HT elicits a wide spectrum of stress responses, such as induction of heat shock proteins, protein aggregation and cell death in mammalian cells. Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown.
Identification of common gene networks responsive to mild hyperthermia in human cancer cells.
Specimen part, Cell line, Treatment, Time
View SamplesHyperthermia (HT) is widely used to treat patients with various cancers. In general, HT elicits a wide spectrum of stress responses such as induction of heat shock proteins, protein aggregation and cell death in mammalian cells. Although many biological processes are affected by HT, the overall responses to HT in mammalian cells remain unknown.
Identification of common gene networks responsive to mild hyperthermia in human cancer cells.
Sex, Age, Specimen part, Cell line, Treatment
View SamplesHyperthermia is widely used to treat patients with various cancers. The 42.5C is well known as inflection point of hyperthermia and generally up to 42C of hyperthermia is used in clinical case to combine with other therapy. Here, the effects of heat stress at 42 or 44C for 90 min on the gene expression in HSC-3 human oral squamous carcinoma cells were investigated using an Affymetrix GeneChip system. The cells were treated with heat stress (42 or 44C for 90 min) and followed by incubation for 0, 6, or 12 h at 37C. The percentage of cell death was 5.0 1.5 (mean SD) at 42C for 12 h and 17.4 0.6 at 44C for 12 h. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with heat stress at 42 and 44C.
Gene networks related to the cell death elicited by hyperthermia in human oral squamous cell carcinoma HSC-3 cells.
Cell line, Treatment, Time
View SamplesAlthough an appropriate range of fluoride is thought to be safe and effective, excessive fluoride intake results in toxic effects in either hard tissues of teeth and skeleton or soft tissues of kidney, lung and brain. It is also well known that fluoride at a millimolar range elicits the complex cellular responses such as enzyme activity, signal transduction and apoptosis in many kinds of cells. However, its toxic effects are still unclear.
Genes and gene networks involved in sodium fluoride-elicited cell death accompanying endoplasmic reticulum stress in oral epithelial cells.
Specimen part, Cell line, Treatment, Time
View SamplesAlthough LIPUS has been shown to enhance fracture healing, the underlying mechanism of LIPUS remains to be fully elucidated. Here, to understand the molecular mechanism underlying cellular responses to LIPUS, we investigated gene expression profiles in mouse MC3T3-E1 preosteoblast cells using a GeneChip system.
Genes responsive to low-intensity pulsed ultrasound in MC3T3-E1 preosteoblast cells.
Specimen part, Cell line, Treatment, Time
View SamplesHyperthermia is widely used to treat patients with various cancers. 42.5C is well known as the inflection point of hyperthermia and generally up to 42C of hyperthermia is used in clinical cases combined with other therapies. Here, the effects of heat stress at 42 or 44C for 15 min on the gene expression in human lymphoma U937 cells were investigated using an Affymetrix GeneChip system. The cells were treated with heat stress (42 or 44C for 15 min), followed by incubation for 0, 1, 3 or 6 h at 37C. The percentage of DNA fragmentation was 8.4 2.2 (mean SD) at 42C for 6 h and 21.0 2.0 at 44C for 6 h. Of approximately 47,000 probe sets analyzed, many genes that were differentially expressed by a factor 2.0 or greater were identified in the cells treated with heat stress at 42 and 44C.
Identification of biological functions and gene networks regulated by heat stress in U937 human lymphoma cells.
Specimen part, Cell line, Treatment
View SamplesWe performed global scale microarray analysis to identify detailed mechanisms by which nonpermissive temperature induces cell differentiation in testicular Sertoli TTE3 cells harboring temperature-sensitive SV40 large T-antigen by using an Affymetrix GeneChip system. Testicular Sertoli TTE3 cells used in the present study were derived from transgenic mice harboring a temperature-sensitive simian virus 40 large T-antigen. In the TTE3 cells, inactivation of the T-antigen by a nonpermissive temperature at 39C led to cell differentiation accompanying elevation of transferrin and cyclin-dependent kinase inhibitor CDKN1A. Of the 22, 690 probe sets analyzed, nonpermissive temperature up-regulated 729 probe sets and down-regulated 471 probe sets by >2.0-fold.
Genetic networks in nonpermissive temperature-induced cell differentiation of Sertoli TTE3 cells harboring temperature-sensitive SV40 large T-antigen.
No sample metadata fields
View SamplesBasal cell carcinoma (BCC) is the most frequent malignant tumor of the eyelid. However, there is limited understanding of how altered gene expression of BCC of the eyelid related to the pathogenesis.
Gene networks in basal cell carcinoma of the eyelid, analyzed using gene expression profiling.
Age, Specimen part
View Samples