Interaction of Male Specific Lethal complex and genomic imbalance on global gene expression in Drosophila
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE162951 | GEO | 2021/10/13
REPOSITORIES: GEO
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Project description:Abdominal aortic aneurysms (AAAs) are a prevalent and deadly human pathology with strong sexual dimorphism. Research demonstrates that sex hormones influence, but do not fully explain, male versus female AAA pathology. In addition to sex hormones, the X and Y sex chromosomes, and their unique complements of genes, may contribute to sexually dimorphic AAA pathology. Here, for the first time, we defined the effect of female (XX) versus male (XY) chromosome complement on AAA formation and rupture in phenotypically female mice using an established murine model. Abdominal aortas from female mice bearing the XY chromosome selectively expressed Y chromosome genes, while genes known to escape X-inactivation were higher in XX females. The majority of gene differences in XY females fell within inflammatory pathways. When XY females were infused with AngII, AAA incidences doubled and aneurysms ruptured. AAAs from XY females exhibited significant inflammation. Moreover, infusion of AngII to XY females augmented aortic activity of matrix metalloproteinases. Finally, testosterone exposure applied chronically, or as a single bolus at postnatal day 1, markedly worsened AAA outcomes in XY compared to XX females. These results demonstrate that an XY sex chromosome complement profoundly influences aortic gene expression profiles and promotes AAA severity.
2016-11-07 | GSE81580 | GEO
Project description:MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males in order to equalize expression of X-linked genes between males (XY) and females (XX). The increase in transcript levels correlates with MSL- dependent acetylation of histone H4 at K16 within the bodies of active genes, but identification of the transcriptional step affected has not been possible. In this study, we use global run-on sequencing (GRO-seq) to examine the specific effect of MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific control may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome. Global Run-On Sequencing (GRO-Seq) reads, i.e., RNA-Seq of nascent RNA transcripts, from D. Melanogaster SL2 cells. Two biological replicates of cells treated with control GFP RNAi and cells treated with MSL2 RNAi were analyzed.
2011-03-03 | E-GEOD-25887 | biostudies-arrayexpress
Project description: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. The MSL2 protein is essential component of the MSL complex. MSL2 is the only protein that is strictly limited to males. MSL2 together with MSL1 forms the core of the MSL complex. The global effect of msl2 mutation on gene expression was measured by microarray analysis. We found that expression of the X chromosome was decreased in msl21 male larvae, supporting the involvement of MSL2 in the up-regulation of X-linked genes. However, there was no change in expression of 4th chromosomal and heterochromatic genes. This finding is broadly comparable to reports of reduced X chromosome expression following msl2 RNAi knockdown in S2 cells. Hence MSL2 is required for up-regulation of male X chromosome where as it is not necessary for normal expression of 4th chromosomal genes and heterochromatic genes in Drosophila melanogaster males.
2009-08-03 | GSE12054 | GEO
Project description:We used H83M2 P element to ectopically expressed MSL2 protein in females to test if the novel formed MSL complex is the directly reason of dosage compensation Compare the MSL2 females with normal females and normal males; MSL2 males also included.
2012-10-16 | E-GEOD-41570 | biostudies-arrayexpress
Project description:In Drosophila, the global increase in transcription from the X chromosome in males to compensate for its monosomy is mediated by the male-specific-lethal complex (MSL-C) consisting of five proteins and two non-coding RNAs, roX1 and roX2. After an initial sequence dependent recognition by the MSL-C of 150-300 high affinity sites, the spreading to the majority of the X-linked genes depends on local MSL-C concentration and active transcription. Here we ask whether any additional RNA species are associated to the MSL-C. No additional roX were found but a strong association was found between the msl2 mRNA and the MSL-C. Based on our results we propose a model in which a non-chromatin associated partial or complete MSL-C titrates newly transcribed msl2 mRNA and thus feed-back regulates the amount of available MSL-C. In total 12 samples; 4 Input files (4 different conditions) with the corresponding 8 RIP samples (2 different antibodies, same 4 conditions as Input)
2011-04-13 | E-GEOD-20249 | biostudies-arrayexpress
Project description:We have studied the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by binding to promoters as well as TSS-distal enhancer regions. In contrast to flies, the MSL complex is not enriched on the X chromosome yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix ncRNA, the major repressor of Xist lncRNA. MSL depletion leads to severely decreased Tsix expression, reduced REX1 recruitment, and consequently accumulation of Xist RNA in ESCs. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs. We have performed ChIP-seq of KANSL3, MCRS1, MOF, MSL1 and MSL2 in mouse ESCs, and KANSL3, MOF and MSL2 in NPCs, in duplicate and normalised against their inputs. We have also performed RNA-seq following knockdown of Kansl3, Mof, Msl1 and Msl2 mouse embryonic stem cells in triplicate. NB: Kansl3 and Mof knockdown-RNAseq are analyzed against their own scrambled controls, and Msl1 and Msl2 against another scrambled control triplicate.
2014-06-03 | E-GEOD-57698 | biostudies-arrayexpress
Project description:In Drosophila, the global increase in transcription from the X chromosome in males to compensate for its monosomy is mediated by the male-specific-lethal complex (MSL-C) consisting of five proteins and two non-coding RNAs, roX1 and roX2. After an initial sequence dependent recognition by the MSL-C of 150-300 high affinity sites, the spreading to the majority of the X-linked genes depends on local MSL-C concentration and active transcription. Here we ask whether any additional RNA species are associated to the MSL-C. No additional roX were found but a strong association was found between the msl2 mRNA and the MSL-C. Based on our results we propose a model in which a non-chromatin associated partial or complete MSL-C titrates newly transcribed msl2 mRNA and thus feed-back regulates the amount of available MSL-C.
2011-04-13 | GSE20249 | GEO
Project description:Objective-Aortic pathologies exhibit sexual dimorphism, with aneurysms in the ascending, thoracic and abdominal aorta (AAA) exhibiting higher prevalence in males. Despite lower incidence of aortic vascular disease in women, aneurysms progress rapidly. Mechanisms for these sex differences are unclear. We defined the role of sex chromosome complement and testosterone in regional development and progression of angiotensin II (AngII)-induced vascular pathologies. Approach and Results-We used transgenic male mice expressing Sry on an autosome to create low density lipoprotein receptor (Ldlr) deficient male mice with an XY or XX sex chromosome complement. Subjects were then sham operated or orcheictomized. Transcriptional profiling on abdominal aortas from XY or XX males demonstrated1746 genes influenced by sex chromosomes, sex hormones, or an interaction. A second cohort of animals was then infused with AngII for 28 days. Diffuse aortic aneurysm pathology developed in XY AngII-infused males, while XX males developed discrete AAAs. Castration reduced all AngII-induced aortic pathologies in XY and XX males. Thoracic aortas from AngII-infused XY males, but not XX males exhibited adventitial thickening. We infused male XY and XX mice with saline or AngII and quantified mRNA abundance of key genes in thoracic versus abdominal aortas. Regional differences in mRNA abundance existed before AngII infusions, which were differentially influenced by AngII between genotypes. Prolonged AngII infusions resulted in AAA aortic wall thickening in XY males with diffuse aortic pathology, while XX males had dilated focal AAAs. Conclusions-An XY sex chromosome complement mediates diffuse aortic pathology, while an XX sex chromosome complement contributes to discrete AngII-induced AAAs.
2018-07-22 | GSE102143 | GEO
Project description:The Drosophila male-specific lethal (MSL) complex binds to the male X chromosome to activate transcription, and consists of five proteins, MSL1, MSL2, MSL3, MOF, MLE, and two roX RNAs. The MLE helicase remodels the roX lncRNAs, enabling the lncRNA-mediated assembly of the Drosophila dosage compensation complex. MSL2 is expressed only in males and interacts with the N-terminal zinc-finger of the transcription factor CLAMP that is important for specific recruitment of the MSL complex on the male X chromosome. Here we found that the unstructured C-terminal region of MLE interacts with 6-7 zinc-finger domains of CLAMP. In vitro 4-5 zinc fingers are critical for specific DNA-binding of CLAMP with GA-repeats, which constitute the core motif at the high affinity binding sites for MSL proteins. Deletion of the Clamp Binding Domain (CBD) in MLE results in decreasing of MSL proteins association with male X chromosome and increasing of male lethality. These results suggest that interactions of unstructured regions in MSL2 and MLE with CLAMP zinc finger domains are important for the specific recruitment of the MSL complex on the male X chromosome.
2024-03-20 | GSE239354 | GEO
Project description: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. The MSL2 protein is essential component of the MSL complex. MSL2 is the only protein that is strictly limited to males. MSL2 together with MSL1 forms the core of the MSL complex. The global effect of msl2 mutation on gene expression was measured by microarray analysis. We found that expression of the X chromosome was decreased in msl21 male larvae, supporting the involvement of MSL2 in the up-regulation of X-linked genes. However, there was no change in expression of 4th chromosomal and heterochromatic genes. This finding is broadly comparable to reports of reduced X chromosome expression following msl2 RNAi knockdown in S2 cells. Hence MSL2 is required for up-regulation of male X chromosome where as it is not necessary for normal expression of 4th chromosomal genes and heterochromatic genes in Drosophila melanogaster males. Experiment Overall Design: Total RNA was prepared from groups of 50 (or more in case of smaller larvae) third instar larvae by TRIzol (Invitrogen) extraction and purified using the RNeasy kit (Qiagen). Three independent RNA preparations for each genotype served as templates for probe synthesis. Affymetrix Drosophila Genome 2.0 chips were hybridized to these probes (Santa Clara, CA). Affymetrix Gene expression data was background corrected, normalized and summarized into a one expression value per sample and probeset using the RMA (robust multi-array average) algorithm. Changes in gene expression (log2 fold changes) were determined by comparing the mean RMA expression values in the msl21 sample to the mean RMA expression values in the msl21/+ samples.
2009-08-07 | E-GEOD-12054 | biostudies-arrayexpress