This study was aimed at understanding the genome-wide binding and regulatory role of the DAXX transcriptional repressor, recently implicated in PCa. ChIP-Seq analysis of genome-wide distribution of DAXX in PC3 cells revealed over 59,000 DAXX binding sites, found at regulatory enhancers and promoters. ChIP-Seq analysis of DNA methyltransferase 1 (DNMT1), which is a key epigenetic partner for DAXX repression, revealed that DNMT1 binding was restricted to a small number of DAXX sites. DNMT1 and DAXX bound close to transcriptional activator motifs. DNMT1 sites were found to be dependent on DAXX for recruitment by analyzing DNMT1 ChIP-Seq following DAXX knockdown (K/D), corroborating previous findings that DAXX recruits DNMT1 to repress its target genes. Massively parallel RNA sequencing (RNA-Seq) was used to compare the transcriptomes of WT and DAXX K/D PC3 cells. Genes induced by DAXX K/D included those involved in autophagy, and DAXX ChIP-Seq peaks were found close to the transcription start sites (TSS) of autophagy genes, implying they are more likely to be regulated by DAXX. Overall design: Determine changes in gene expression levels between WT and DAXX K/D prostate cancer cells by RNA-Seq (PC3 Cells).
The DAXX co-repressor is directly recruited to active regulatory elements genome-wide to regulate autophagy programs in a model of human prostate cancer.
No sample metadata fields
View SamplesRegulatory T (Treg) cells play an indispensable role in immune homeostasis. The development and function of Tregs are dependent on transcriptional factor Foxp3, but how constant expression of Foxp3 is maintained in Tregs is not clear. Here we show that ablation of the conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus in mice led to spontaneous lymphoproliferative disease and exacerbation of experimental autoimmune encephalomyelitis (EAE). CNS2 is required for activated Treg cells to maintain elevated Foxp3 expression, which is critical for their suppressor function and lineage stability. Mechanistically, upon TCR stimulation, NFAT binds to both CNS2 and Foxp3 promoter and mediates the interaction between CNS2 and Foxp3 promoter. Our findings demonstrated an essential role for CNS2 in maintaining the stability and function of activated Treg cells and identified NFAT as a key mediator of its function. Overall design: Gene expression was profiled in T regulatory cells (Treg) in WT and CNS2 knockout mice. CNS2 knockout mice lack a conserved non-coding DNA sequence 2 (CNS2) at the Foxp3 locus. Treg cells were further sorted into Foxp3-high and Foxp3-low populations based on the expression level of Foxp3. mRNA was profiled using RNA-Seq (unstranded, polyA+, SE100) in replicate for each condition
Function of a Foxp3 cis-element in protecting regulatory T cell identity.
No sample metadata fields
View SamplesInbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS) mice exhibit a large difference in a number of alcohol and drug related behaviors. This study examined the expression levels of transcripts in these strains in the cerebellum, which is a major target of ethanols actions in the CNS, in order to find differentially expressed candidate genes for these phenotypes. Cerebellum was specifically chosen due to the fact that Purkinje cell sensitivity to ethanol in these strains is highly correlated to "sleep time", the measure of ethanol sensitivity used with these strains. Naive mice were used because differences in sensitivity are observed upon initial exposure to ethanol.
Expression profiling identifies novel candidate genes for ethanol sensitivity QTLs.
Sex, Specimen part
View SamplesThe possible benefits of selenium (Se) supplementation are currently under investigation for prevention of certain cancers and treatment of neurological disorders. Little is known concerning the response of the brain to increased dietary Se under conditions of Se sufficiency, despite the majority of Se supplementation trials occurring in healthy subjects considered Se sufficient. We evaluated the transcriptional response of the zebrafish (Danio rerio) brain to supplementation with nutritionally relevant levels of dietary Se (sodium selenite) during conditions of assumed Se sufficiency.
Sex-specific transcriptional responses of the zebrafish (Danio rerio) brain selenoproteome to acute sodium selenite supplementation.
Sex, Age, Specimen part, Treatment
View SamplesArabidopsis MPK4 is involved in the control of antagonism between salicylic acid (SA) and ethylene (ET)/jasmonic acid (JA) pathways in the plant innate immune system as a repressor of the SA pathway, but an activator of the ET/JA pathway. Here we and use comparative microarray analysis of ctr1, ctr1/mpk4, mpk4 and wild type to show that MPK4 is required for only a narrow subset of ET regulated genes.
Arabidopsis systemic immunity uses conserved defense signaling pathways and is mediated by jasmonates.
Age, Specimen part
View SamplesStable knockdown of NET1, a RhoGEF, was achieved in AGS Gastric Cancer cells. This gene is known to be overexpressed in the disease.
A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer.
Cell line
View SamplesPurpose: To identify transcriptional changes by RNA-seq in tumor samples, before bevacizumab combination treatment and after bevacizumab combination treatment in both responding and non-responding recurrent glioblastoma patients Overall design: Three comparison analyses were further performed: 1.) Paired analysis of pre- and post-treated samples from responding patients; 2.) Comparison of pre-treated samples of responders vs. non-responders; 3.) Paired analysis of pre- and post-treated samples from non-responding patients The sample ''characteristics: batch'' represents a combination of the RNA-extraction date and the library-preparation date for each sample.
Transcriptional changes induced by bevacizumab combination therapy in responding and non-responding recurrent glioblastoma patients.
Sex, Disease, Disease stage, Subject, Time
View SamplesAs part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from 18-month-old Ahr-knockout and wild-type mice. HSC from aged AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC.
Conditional deletion of Ahr alters gene expression profiles in hematopoietic stem cells.
No sample metadata fields
View SamplesAs part of a study of the role of the aryl hydrocarbon receptor (Ahr) in maintenance and senescence of hematopoietic stem cells (HSC), global gene expression profiling was done with HSC isolated from Ahr-knockout and wild-type mice. HSC from young-adult (8 wk old) AhR-KO mice had changes in expression of many genes related to HSC maintenance, consistent with the phenotype observed in aging Ahr-KO mice: decreased survival rate, splenomegaly, increased circulating white blood cells, hematopoietic cell accumulation in tissues, anemia, increased numbers of stem/progenitor and lineage-committed cells in bone marrow, decreased erythroid progenitor cells in bone marrow, and decreased self-renewal capacity of HSC.
Loss of aryl hydrocarbon receptor promotes gene changes associated with premature hematopoietic stem cell exhaustion and development of a myeloproliferative disorder in aging mice.
Specimen part
View SamplesThe amino acid homocysteine increases in the serum when there is insufficient folic acid or vitamin B12, or with certain mutations in enzymes important in methionine metabolism. Elevated homocysteine is related to increased risk for cardiovascular and other diseases in adults and elevated maternal homocysteine increases the risk for certain congenital defects, especially those that result from abnormal development of the neural crest and neural tube. Experiments with the avian embryo model have shown that elevated homocysteine perturbs neural crest / neural tube migration in vitro and in vivo. While there have been numerous studies of homocysteine-induced changes in gene expression in adult cells, there is no previous report of a homocysteine-responsive transcriptome in the embryonic neural crest. We treated neural crest cells in vitro with exogenous homocysteine in a protocol that induces significant changes in neural crest cell migration. We used microarray analysis and expression profiling to identify 65 transcripts of genes of known function that were altered by homocysteine. The largest set of effected genes (19) included those with a role in cell migration and adhesion. Other major groups were genes involved in metabolism (13); DNA / RNA interaction (11); cell proliferation / apoptosis (10); and transporter / receptor (6). Although the genes identified in this experiment were consistent with prior observations of the effect of homocysteine upon neural crest cell function, none had been identified previously as response to homocysteine in adult cells.
Microarray analysis of homocysteine-responsive genes in cardiac neural crest cells in vitro.
No sample metadata fields
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