Because it excises thymine from GT mismatches, TDG was proposed to counter mutagenesis by 5-methylcytosine deamination. Yet, TDG was also observed to attack 5-methycytosine itself, making it a candidate DNA demethylase, and interactions with transcription factors implicated additional functions in gene regulation. Unlike other DNA glycosylases, TDG is essential for embryonic development. Fibroblasts from Tdg null embryos show massively impaired gene regulation, and this correlates with imbalanced histone modification and CpG methylation. TDG associates with the promoters of affected genes in MEFs and in embryonic stem cells, but epigenetic aberrations appear only in differentiated cells. TDG also contributes to the maintenance of active and bivalent chromatin during cell differentiation, using its DNA glycosylase activity to counter aberrant de novo methylation. Thus, TDG dependent DNA repair stabilizes epigenetic states during cell differentiation.
Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability.
Specimen part
View SamplesAndrogens are essential for sexual development and reproduction. However, androgen regulation in health and disease is poorly understood. Previously, we showed that human adrenocortical H295R cells grown under starvation conditions acquire a hyperandrogenic steroid profile with changes in steroid metabolizing enzymes HSD3B2 and CYP17A1 essential for androgen production. Furthermore, we have shown that metformin inhibits androgen production of steroidogenic H295R cells and inhibits complex I activity of the respriatory chain. Therefore, to search for underlying mechanisms regulting androgen production and to understand the basic biology of androgens, we have characterized the gene expression profile of H295R cells grown under normal growth conditions, serum starvation (hyperandrogenic) growth conditions as well as after metformin treatment (hypoandrogenic).
Retinoic acid receptor beta and angiopoietin-like protein 1 are involved in the regulation of human androgen biosynthesis.
Cell line
View SamplesReduced oxygen availability during embryogenesis leads to intra-uterine growth restriction (IUGR), increasing the risk for hypertension, cardiovascular and chronic kidney disease (CKD) in adults. Although this association has long been recognized, underlying mechanisms still require extensive research.
Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.
Treatment
View SamplesThe contribution of aberrant DNA methylation and the downstream effects in tumorogenesis through silencing of tumor suppressor genes (TSGs) and microRNAs has been investigated. Since these epigenetic alterations can be reversed, we investigated the effects of the epigenetic therapy in breast cancer cell lines.
Integrated epigenetics of human breast cancer: synoptic investigation of targeted genes, microRNAs and proteins upon demethylation treatment.
Treatment
View SamplesRhoH/TTF is upregulated in eosinophils by exposure to cytokines. To find out which genes are regulated by RhoH, we investigated changes in gene expression in eosinophilic HL-60c15 cells overexpressing RhoH
No associated publication
Cell line, Treatment
View SamplesThe objective of this study was to compare the transcriptional repertoire of mature human neutrophils before and after GM-CSF treatment by using oligonucleotide microarrays.
RhoH/TTF negatively regulates leukotriene production in neutrophils.
Specimen part
View SamplesCurrent methods to analyze gene expression measure steady-state levels of mRNA. In order to specifically analyze mRNA transcription, a technique has been developed that can be applied in-vivo. The technique is referred with the acronym NIAC-NTR (Non Invasive Application and Capture of Newly Transcribed RNA). This method makes use of the cellular pyrimidine salvage pathway and is based on affinity-chromatographic isolation of thiolated mRNA. When combined with data on mRNA steady-state levels, this method is able to assess the relative contributions of mRNA synthesis and degradation/stabilization. It overcomes limitations associated with currently available methods such as mechanistic intervention that disrupts cellular physiology, or the inability to apply the techniques in-vivo. The method has been applied to a model of serum response of cultured primary mouse embryonic fibroblasts.
Microarray analysis of newly synthesized RNA in cells and animals.
No sample metadata fields
View SamplesCurrent methods to analyze gene expression measure steady-state levels of mRNA. In order to specifically analyze mRNA transcription, a technique has been developed that can be applied in-vivo in intact cells and animals. The technique is referred with the acronym NIAC-NTR (Non Invasive Application and Capture of Newly Transcribed RNA). This method makes use of the cellular pyrimidine salvage pathway and is based on affinity-chromatographic isolation of thiolated mRNA. When combined with data on mRNA steady-state levels, this method is able to assess the relative contributions of mRNA synthesis and degradation/stabilization. It overcomes limitations associated with currently available methods such as mechanistic intervention that disrupts cellular physiology, or the inability to apply the techniques in-vivo. The method was applied to study renal ischemia reperfusion injury, demonstrating its applicability for whole organs in-vivo.
Microarray analysis of newly synthesized RNA in cells and animals.
Age
View SamplesExpression data from specific translational activity and cytoplasmic localization (nuclear retention) of mRNAs of primary mouse embryonic fibroblasts (MEF) early in response to serum.
No associated publication
No sample metadata fields
View Samples