Drosophila males double transcription of their single X chromosome to equalize X-linked gene expression with females, which carry two X chromosomes. Increased transcription requires the Male-Specific Lethal (MSL) complex. One of the primary functions of the MSL complex is thought to be enrichment of H4Ac16 on the male X chromosome, a modification linked to elevated transcription. The roX1 and roX2 RNAs are essential but redundant components of the MSL complex. Simultaneous removal of both roX RNAs reduces MSL X-localization and leads to ectopic binding of these proteins at autosomal sites and to the chromocenter. Some H4Ac16 accumulates at these ectopic sites in roX1- roX2- males, suggesting the possibility of increased expression. The global effect of roX mutations on gene expression was measured by microarray analysis. We found that expression of the X chromosome was decreased by 26% in roX1- roX2- male larvae, supporting the involvement of roX RNAs in the up-regulation of X-linked genes. This finding is broadly comparable to reports of reduced X chromosome expression following msl2 RNAi knockdown in S2 cells. In spite of strong MSL binding and H4Ac16 accumulation at autosomal sites in roX1- roX2- males, enhanced gene expression could not be detected at these sites by microarray analysis or reverse northern blotting. Thus, failure to compensate X-linked genes, rather than inappropriate up-regulation of autosomal genes at ectopic sites of MSL binding, appears to cause male lethality upon loss of roX RNAs.
roX RNAs are required for increased expression of X-linked genes in Drosophila melanogaster males.
Sex
View SamplesroX RNAs are involved in the chromosome-wide gene regulation that occurs during dosage compensation in Drosophila. Dosage compensation equalizes expression of X-linked and autosomal genes. Drosophila males increase transcription two-fold from their single X chromosome. This is mediated by the MSL complex, which is composed of the male-specific lethal (MSL) proteins and two noncoding roX RNAs, roX1 and roX2. Upon elimination of both roX transcripts, a global decrease of X-linked gene expression is observed in males. Expression of the genes on the entire 4th chromosome also decreased in the absence of both roX transcripts. roX1 RNA also presents in females in the early stages. To investigate the effect of loss of roX transcripts on gene expression in females, gene expression was analyzed by microarrays in roX1-roX2- female flies. To eliminate inconsistency caused by differences in genetic background, expression of roX1-roX2- females with females of virtually identical genetic background but carrying the [hsp83-roX1+] transgene were compared. Expression of any chromosome did not change in roX1-roX2- females. It was concluded that roX RNAs only effect in males .
Coordinated regulation of heterochromatic genes in Drosophila melanogaster males.
Sex
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Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Age, Specimen part
View SamplesTranscriptomic analysis of FACS-sorted Pax7nGFP quiescent skeletal muscle satellite cells cells from young, and old mice. Results provide knowledge about the molecular mechanisms underlying age-related skeletal muscle satellite cells homeostasis.
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Specimen part
View SamplesTranscriptomic analysis of FACS-sorted Pax7nGFP quiescent skeletal muscle satellite cells cells from old, and post-mortem mice. Results provide knowledge about the molecular mechanisms underlying age-related skeletal muscle satellite cells homeostasis.
Distinct metabolic states govern skeletal muscle stem cell fates during prenatal and postnatal myogenesis.
Age, Specimen part
View SamplesExpression of DREAM in dorsal root ganglia and spinal cord is related to endogenous control mechanisms of acute and chronic pain. In primary sensory trigeminal neurons high levels of endogenous DREAM protein are preferentially localized in the nucleus, suggesting a major transcriptional role. Here, we show that DREAM participates in the control of trigeminal pain perception through the regulation of prodynorphin and BDNF. Furthermore, genome-wide analysis of trigeminal neurons in daDREAM transgenic mice revealed that cathepsin L (CTSL) and the monoglyceride lipase (MGLL) are new DREAM downstream targets and have a role in the regulation of trigeminal nociception.
Transcriptional repressor DREAM regulates trigeminal noxious perception.
Specimen part
View SamplesDocetaxel-based chemotherapy is the standard first-line therapy in metastatic castration-resistant prostate cancer. However, most patients eventually develop resistance to this treatment.
Identification of docetaxel resistance genes in castration-resistant prostate cancer.
Disease, Disease stage, Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms.
Cell line, Treatment
View SamplesHCT116 microarray done 12 hours after treatment with DMSO (control) or Nutlin
Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms.
Cell line, Treatment
View Samples5-hydroxymethylcytosine (5hmC) occurs at maximal levels in postmitotic neurons where its accumulation is cell specific and correlated with gene expression. Here we demonstrate that the distribution of 5hmC in CG and non-CG dinucleotides is distinct, and that it reflects the binding specificity and genome occupancy of methylcytosine binding protein 2 (MeCP2). In expressed gene bodies, accumulation of 5hmCG acts in opposition to 5mCG resulting in “functional” demethylation and diminished MeCP2 binding, thus facilitating transcription. Non-CG hydroxymethylation occurs predominantly in CA dinucleotides (5hmCA) and it accumulates in regions flanking active enhancers. In these domains, oxidation of 5mCA to 5hmCA does not alter MeCP2 binding or expression of adjacent genes. We conclude that the role of 5-hydroxymethylcytosine in postmitotic neurons is to functionally demethylate expressed gene bodies while retaining the role of MeCP2 in chromatin organization. Overall design: Examination of genome wide cytosine methylation and hydroxymethylation per context in cerebellar granule cells and their function in MeCP2 binding. Nuclear RNA-Seq dataset.
5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes.
Cell line, Subject
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