Acetyltransferases and histone deacetylases regulate gene expression at the level of chromatin, mainly by affecting transcription. In this study, we report that hyperacetylation induced by inhibition of histone deacetylases (HDACs) causes massive degradation of mRNA. The effect is promoter-independent and affects poly-A mRNA globally. HDAC inhibition leads to the removal of poly-A tails from mRNAs through activation of the deadenylase CAF1a, which we find to be acetylated together with its activator BTG2 by the histone acetyl transferases (HATs) p300 and CBP. By mutation of critical lysine residues, we provide evidence that acetylation of CAF1a and BTG2 induces enhanced poly-A mRNA degradation. Our study reveals a fundamental mechanism by which cells coordinate epigenetic and transcriptional control of gene expression with posttranscriptional control of poly-A mRNA stability. In this experiment, HeLa cells were exposed to the HDAC inhibitor trichostatin A (TSA) for 16 hours, followed by treatment with actinomycin D. Total RNA was isolated after 0, 2, 4 and 6 hours, and analysed by RNA sequencing. The half-lives of 7431 RNAs were calculated after normalization to rRNA (18S + 28S) levels. The experiment shows that TSA treatment causes a general reduction of poly-A RNA stability, while replication-dependent histone mRNA stability is not affected. Overall design: RNA half-lives were measured in TSA-treated or untreated HeLa cells by RNA-Seq using Illumina HiSeq 2000.
Acetylation-Dependent Control of Global Poly(A) RNA Degradation by CBP/p300 and HDAC1/2.
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Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sex, Specimen part
View SamplesThere is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology.
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sex, Specimen part
View SamplesThere is an ongoing debate on the potential toxicity of genetically modified food. The ability of rodent feeding trials to assess the potential toxicity of these products is highly debated since a 2-year study in rats fed NK603 Roundup-tolerant genetically modified maize, treated or not with Roundup during the cultivation, resulted in anatomorphological and blood/urine biochemical changes indicative of liver and kidney structure and functional pathology.
Transcriptome and metabolome analysis of liver and kidneys of rats chronically fed NK603 Roundup-tolerant genetically modified maize.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.
Sex, Specimen part
View SamplesGlyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH residues pose a particular risk to the kidneys and liver. However, the existence of biological effects with negative health implications at low environmentally relevant doses remains unresolved. A previous investigation addressed this issue, by conducting a 2-year feeding study, which included 10 female Sprague Dawley rats administered via drinking water with 0.1 ppb of a major Roundup formulation (50 ng/L glyphosate equivalent dilution). Hepatorenal toxicities, as well as urine and blood biochemistry disturbances at the 15th month of age were observed. In an effort to obtain molecular mechanistic insight into the underlying causes of these pathologies, we have carried out a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 genes were found to be disturbed respectively in liver and kidney (p<0.01, q<0.08, fold change >1.1). Among the 1319 genes whose expression was altered in both tissues, 3 functional categories were over-represented. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. The transcription factor networks that can account for these disruptions were centered on CREB1, ESR1, YY1, c-Myc and Oct3/4 activity, which are known to closely cooperate in the regulation of gene expression after hormonal stimulation. The analysis of pathways and toxicity processes showed that these disturbances in gene expression were representative of fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with the pathologies observed at an anatomical and histological level. Our results suggest that new studies incorporating testing principles from endocrinology and developmental epigenetics need to be performed to investigate potential consequences of exposure to low dose, environmental levels of GBH and glyphosate.
Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.
Sex, Specimen part
View SamplesGlyphosate-based herbicides (GBH) are the major pesticides used worldwide. Converging evidence suggests that GBH residues pose a particular risk to the kidneys and liver. However, the existence of biological effects with negative health implications at low environmentally relevant doses remains unresolved. A previous investigation addressed this issue, by conducting a 2-year feeding study, which included 10 female Sprague Dawley rats administered via drinking water with 0.1 ppb of a major Roundup formulation (50 ng/L glyphosate equivalent dilution). Hepatorenal toxicities, as well as urine and blood biochemistry disturbances at the 15th month of age were observed. In an effort to obtain molecular mechanistic insight into the underlying causes of these pathologies, we have carried out a transcriptome microarray analysis of the liver and kidneys from these same animals. The expression of 4224 and 4447 genes were found to be disturbed respectively in liver and kidney (p<0.01, q<0.08, fold change >1.1). Among the 1319 genes whose expression was altered in both tissues, 3 functional categories were over-represented. First, genes involved in mRNA splicing and small nucleolar RNA were mostly upregulated, suggesting disruption of normal spliceosome activity. Electron microscopic analysis of hepatocytes confirmed nucleolar structural disruption. Second, genes controlling chromatin structure (especially histone-lysine N-methyltransferases) were mostly upregulated. Third, genes related to respiratory chain complex I and the tricarboxylic acid cycle were mostly downregulated. The transcription factor networks that can account for these disruptions were centered on CREB1, ESR1, YY1, c-Myc and Oct3/4 activity, which are known to closely cooperate in the regulation of gene expression after hormonal stimulation. The analysis of pathways and toxicity processes showed that these disturbances in gene expression were representative of fibrosis, necrosis, phospholipidosis, mitochondrial membrane dysfunction and ischemia, which correlate with the pathologies observed at an anatomical and histological level. Our results suggest that new studies incorporating testing principles from endocrinology and developmental epigenetics need to be performed to investigate potential consequences of exposure to low dose, environmental levels of GBH and glyphosate.
Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure.
Sex, Specimen part
View SamplesIn order to identify pre-conceptional endometrial dysregulations, we compared the endometrial expression between fertile and IF and RM patients
Specific and extensive endometrial deregulation is present before conception in IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages.
Sex, Specimen part
View SamplesDetermination of the genes regulated by ERRalpha nuclear receptor in MDA-MB231 cells Overall design: MDA-MB231 cells were inactivated for ERRalpha using siRNA. Three different siRNAs were used (siE1, siE2, siE3). Cells treated with a control siRNA (siC samples) were used for comparison. Duplicate samples were analyzed. Transcriptomic analysis was performed by RNA-Seq
ERRα induces H3K9 demethylation by LSD1 to promote cell invasion.
Cell line, Subject
View SamplesDetermination of the genes regulated by LSD1 in MDA-MB231 cells Overall design: MDA-MB231 cells were inactivated for LSD1 using siRNA. Two different siRNAs were used (siL1, siL2). Cells treated with a control siRNA (siC samples) were used for comparison. Duplicate samples were analyzed. Transcriptomic analysis was performed by RNA-Seq
ERRα induces H3K9 demethylation by LSD1 to promote cell invasion.
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