In addition to its essential metabolic functions biotin is suggested a critical role in regulating gene expression. The first committed enzyme in biotin biosynthesis in Arabidopsis, 7-keto-8-aminopelargonic acid synthase is encoded by At5g04620 (BIO4). We isolated a novel T-DNA insertion mutant of BIO4 (bio4-1) showing a spontaneous cell death phenotype that could be rescued both by exogenous biotin and genetic complementation. The bio4-1 plants exhibited massive accumulation of hydrogen peroxide.
Biotin deficiency causes spontaneous cell death and activation of defense signaling.
Age, Specimen part
View SamplesAn early settlement of a complex gut microbiota can protect against gastro-intestinal dysbiosis, but the effects of neonatal microbiota colonization on the gut barrier upon the further encounter of favorable bacteria or not, are largely unknown.
Molecular networks affected by neonatal microbial colonization in porcine jejunum, luminally perfused with enterotoxigenic Escherichia coli, F4ac fimbria or Lactobacillus amylovorus.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner.
Cell line, Treatment
View SamplesAndrogen receptor (AR) plays an important regulatory role during prostate cancer development. ARs transcriptional activity is regulated by androgenic ligands, but also by post-translational modifications. To study the role of the AR SUMOylation in genuine chromatin environment, we compared androgen-regulated gene expression and AR chromatin occupancy in PC-3 prostate cancer and HEK293 cell lines stably expressing wild-type (wt) or SUMOylation site-mutated AR (AR-K386R,K520R). Our genome-wide gene expression analyses reveal that the SUMOylation modulates the AR function in a target gene and pathway selective manner. The transcripts that are differentially regulated by androgen and SUMOylation are linked to cellular movement, cell death, cellular proliferation, cellular development and cell cycle. In line with these data, SUMOylation mutant AR cells proliferate faster and are more sensitive to apoptosis. Moreover, ChIP-seq analyses show that the SUMOylation modulates the chromatin occupancy of AR on many loci in a fashion that parallels with their differential androgen-regulated expression. De novo motif analyses show that other transcription factor-binding motifs are differentially enriched at the wtAR- and the AR-K386R,K520R-preferred genomic binding positions. Taken together, our data indicate that SUMOylation does not simply repress the AR activity, but it regulates ARs interaction with the chromatin and the receptors target gene selection.
SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Cell line, Treatment, Time
View SamplesForced sustained swimming exercise at optimal speed enhances growth in many fish species, particularly through hypertrophy of the white skeletal muscle. The exact mechanism of this effect has not been resolved yet. To explore the mechanism, we first subjected wild-type zebrafish to an exercise protocol validated for exercise-enhanced growth, and showed that exercised zebrafish, which indeed showed enhanced growth, had higher cortisol levels than the non-exercised controls. A central role was therefore hypothesized for the steroid hormone cortisol acting through the Glucocorticoid receptor (Gr). Second, we subjected wild-type zebrafish and zebrafish with a mutant Gr to exercise at optimal, suboptimal and super-optimal speeds and compared them with non-exercised controls. Exercised zebrafish showed growth enhancement at all speeds, with highest growth at optimal speeds. In the Gr mutant fish, exercise resulted in growth enhancement similar to wild-type zebrafish, indicating that cortisol cannot be considered as a main determinant of exercise-enhanced growth. Finally, the transcriptome of white skeletal muscle tissue was analysed by RNA sequencing. The results of this analysis showed that in the muscle tissue of Gr mutant fish a lower number of genes is regulated by exercise than in wild-type fish (183 versus 351). A cluster of 36 genes was regulated by exercise in both wild-type and mutant fish. In this cluster, genes involved in transcriptional regulation and protein ubiquitination were overrepresented. Since growth was enhanced similarly in both wild-type fish and mutants, these processes may play an important role in exercise-enhanced growth. Overall design: Deep-sequencing transcriptome analysis of white muscle samples derived from wild-type (++) or glucocorticoid receptor (Gr) mutant (--) Danio rerio specimens that were exposed to either a resting (REST) or a swimming (UOPT) regimen: wild-type resting (REST++; n=3), Gr mutant resting (REST--; n=3), wild-type swimming (UOPT++; n=3), Gr mutant swimming (UOPT--; n=3).
Cortisol Acting Through the Glucocorticoid Receptor Is Not Involved in Exercise-Enhanced Growth, But Does Affect the White Skeletal Muscle Transcriptome in Zebrafish (<i>Danio rerio</i>).
Specimen part, Treatment, Subject
View SamplesIn addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and down-regulated genes are affected by the GR sumoylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion which parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, genome-wide SUMO-2/3 marks, which were generally associated with active chromatin, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth.
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Cell line, Treatment, Time
View SamplesIn addition to the glucocorticoids, the glucocorticoid receptor (GR) is regulated by post-translational modifications, including SUMOylation. We have analyzed how SUMOylation influences the activity of endogenous GR target genes and the receptor chromatin binding by using isogenic HEK293 cells expressing wild-type GR (wtGR) or SUMOylation-defective GR (GR3KR). Gene expression profiling revealed that both dexamethasone up- and down-regulated genes are affected by the GR sumoylation and that the affected genes are significantly associated with pathways of cellular proliferation and survival. The GR3KR-expressing cells proliferated more rapidly and their anti-proliferative response to dexamethasone was less pronounced than in the wtGR-expressing cells. ChIP-seq analyses indicated that the SUMOylation modulates the chromatin occupancy of GR on several loci associated with cellular growth in a fashion which parallels with their differential dexamethasone-regulated expression between the two cell lines. Moreover, genome-wide SUMO-2/3 marks, which were generally associated with active chromatin, showed markedly higher overlap with the wtGR cistrome than with the GR3KR cistrome. In sum, our results indicate that the SUMOylation does not simply repress the GR activity, but regulates the activity of the receptor in a target locus selective fashion, playing an important role in controlling the GR activity on genes influencing cell growth.
SUMOylation regulates the chromatin occupancy and anti-proliferative gene programs of glucocorticoid receptor.
Cell line, Treatment, Time
View SamplesDuring sexual dimorphism, the loss of one entire X chromosome in Drosophila males is achieved largely via a broad genome-wide aneuploid effect. Exploring how MSL proteins and two large non coding RNAs (roX1 and roX2) modulate trans-acting aneuploid effect for equality to females, we employ a system biology approach (microarray) to investigate the global aneuploid effect of maleless(mle) mutation by disrupting MSL binding. A large number of the genes (144) that encode a broad spectrum of cellular transport proteins and transcription factors are located in the autosomes of Drosophila melanogaster.
Drosophila maleless gene counteracts X global aneuploid effects in males.
No sample metadata fields
View SamplesCytochrome oxydases and quinol monooxygenase were removed from the E. coli genome resulting in oxygen-independent physiology
Deletion of genes encoding cytochrome oxidases and quinol monooxygenase blocks the aerobic-anaerobic shift in Escherichia coli K-12 MG1655.
No sample metadata fields
View Samples