DNA methylation is thought to induce a transcriptional silencing through the combination of two mechanisms: the repulsion of transcriptional activators that do not recognize their binding sites when methylated, and the recruitment of transcriptional repressors that specifically bind methylated DNA. Methyl CpG Binding Domain proteins MeCP2, MBD1 and MBD2 belong to the latter category. However, the exact contribution of each protein in the DNA methylation dependent transcriptional repression occurring during development and diseases remains elusive. Here we present MBD2 ChIPseq data generated from the endogenous protein in an isogenic cellular model of human mammary oncogenic transformation. In immortalized or transformed cells, MBD2 was found in one fourth of methylated regions and associated with transcriptional silencing. Depletion of MBD2 induces upregulations of genes bound by MBD2 and methylated in their transcriptional start site regions. MBD2 was partially redistributed on methylated DNA during oncogenic transformation, independently of DNA methylation changes. Genes downregulated during this transformation preferentially gained MBD2 binding sites on their promoter. Depletion of MBD2 in transformed cells induced the upregulation of some of these repressed genes, independently of the strategy used for the abrogation of oncosuppressive barriers. Our data confirm that MBD2 is a major interpret of DNA methylation, and show an unreported dynamic in this interpretation during oncogenic transformation. Overall design: RNAseq of untreated HMEC-hTERT cells, siCtrl, siMBD2 or DAC treated HMLER cells, siCtrl or siMBD2 treated HME-ZEB1-RAS and HME-shP53-RAS cells, in duplicates.
Dynamics of MBD2 deposition across methylated DNA regions during malignant transformation of human mammary epithelial cells.
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View SamplesHCN4 channels are the major HCN channel isoform expressed in the sinoatrial node (SAN) and play a key role in cardiac pacemaking. We have characterized the gene expression profile in the SAN of adult mice expressing cAMP-insensitive HCN4 channels (HCN4FEA mice) in comparison to WT mice.
cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells.
Sex, Specimen part
View SamplesWe advance a three gene model of arsenate tolerance in rice based on testing root growth of 108 recombinant inbred lines (RILs) of the Bala x Azucena population. Marker genotype at 3 loci determined arsenate tolerance in 99% of RILs tested. Interestingly, plants must inherit 2, but any two alleles from the tolerant parent (Bala) to have the tolerant phenotype. Challenging the Affymetrix GeneChip Rice Genome array with Azucena and Bala RNA isolated from control and arsenate treated plants revealed 592 genes 2 fold-upregulated by arsenate and 696 downregulated. The array data was also used to identify which genes are expressed within the three target loci.
Rice-arsenate interactions in hydroponics: whole genome transcriptional analysis.
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View SamplesSevere loss-of-function alleles of DCL1 are embryonic lethal. Defects in cell division were seen as early as the globular stage in the strong loss-of-function allele dcl1-15. Phenotypic work with dcl1-15 and the null allele dcl1-5 suggested that, in addition to the severe patterning defects, the mutants were maturing earlier than wild-type embryos.
MicroRNAs regulate the timing of embryo maturation in Arabidopsis.
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View SamplesGlobal transcriptome patterns were determined in XVE-14 and wild-type seedlings induced for 45 min b-estradiol in order to identify the genes early regulated by EBE transcription factor.
EBE, an AP2/ERF transcription factor highly expressed in proliferating cells, affects shoot architecture in Arabidopsis.
Specimen part
View SamplesResveratrol, a natural phytoestrogen found in red wine and a variety of plants, is reported to have protective effects against lung cancer, however there is very little work directed towards the understanding of the mechanism of action of resveratrol in lung cancer. In this study we used an experimental approach to understand the biological activity and molecular mechanisms of resveratrol in A549 lung cancer cells. Gene expression profiles were compiled using an oligonucleotide microarray to determine altered expression levels in resveratrol treated cells.
Molecular mechanisms of resveratrol action in lung cancer cells using dual protein and microarray analyses.
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View SamplesRationale: Obstructive sleep apnea (OSA) has been associated with a number of chronic disorders that may improve with effective therapy. However, the molecular pathways affected by continuous positive airway pressure (CPAP) treatment are largely unknown. We sought to assess the system-wide consequences of CPAP therapy by transcriptionally profiling peripheral blood leukocytes (PBLs). Methods: Subjects diagnosed with severe OSA were treated with CPAP, and whole-genome expression measurement of PBLs was performed at baseline and following therapy. We used Gene Set Enrichment Analysis (GSEA) to identify gene sets that were differentially enriched. Network analysis was then applied to identify key drivers of pathways influenced by CPAP. Results: 18 subjects with severe OSA (apnea hypopnea index 30 events/hour) underwent CPAP therapy and microarray analysis of their PBLs. Treatment with CPAP improved AHI, daytime sleepiness and blood pressure but did not affect anthropometric measures. GSEA revealed a number of enriched gene sets, many of which were involved in neoplastic processes and displayed down-regulated expression patterns in response to CPAP. Network analysis identified several densely connected genes that are important modulators of cancer and tumor growth. Conclusions: Effective therapy of OSA with CPAP is associated with alterations in circulating leukocyte gene expression. Functional enrichment and network analyses highlighted transcriptional suppression in cancer-related pathways suggesting potentially novel mechanisms linking OSA with neoplastic signatures.
Treatment of obstructive sleep apnea alters cancer-associated transcriptional signatures in circulating leukocytes.
Treatment, Subject
View SamplesThe purpose of this experiment is to understand which transcripts are differentially expressed following exposure to TCDD.
TCDD inhibits heart regeneration in adult zebrafish.
Treatment
View SamplesThe goal of this study was to identify signaling molecules downstream of CXCR4 in breast cancer cells. For this purpose, we sorted CXCR4-positive and CXCR4-negative cells from MDA-MB-231 breast cancer cell line by flow cytometry and performed microarrays analysis.
ITF2 is a target of CXCR4 in MDA-MB-231 breast cancer cells and is associated with reduced survival in estrogen receptor-negative breast cancer.
Specimen part, Cell line, Treatment
View SamplesGene expression in E coli W3110 strains with either ybaO over-expression (W3110/pcutR) or ybaO deletion (W3110/cutR) were measured with cysteine challenge.
Anaerobic Cysteine Degradation and Potential Metabolic Coordination in Salmonella enterica and Escherichia coli.
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