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Mef2 activity levels differentially affect gene expression during Drosophila muscle development

ABSTRACT: The conserved Mef2 transcription factor is a major regulator of gene expression and differentiation. Recent genomic studies have identified a large number of mef2-regulated target genes with distinct temporal expression profiles during Drosophila myogenesis. However, the question remains as to how a single transcription factor can control such diverse patterns of gene expression. The aim of this project was to investigate whether there are genes with different mef2-requirements for their expression during muscle differentiation in vivo during the development of Drosophila melanogaster. Keywords: allelic series comparison

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE9889 | GEO | 2007/12/31

SECONDARY ACCESSION(S): PRJNA103885

REPOSITORIES: GEO

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Transcription profiling of Drosophila mef2 allelic series reveals mef2 activity levels differentially affect gene expression during muscle development

Project description:The conserved Mef2 transcription factor is a major regulator of gene expression and differentiation. Recent genomic studies have identified a large number of mef2-regulated target genes with distinct temporal expression profiles during Drosophila myogenesis. However, the question remains as to how a single transcription factor can control such diverse patterns of gene expression. The aim of this project was to investigate whether there are genes with different mef2-requirements for their expression during muscle differentiation in vivo during the development of Drosophila melanogaster. Experiment Overall Design: We used microarrays in conjunction with a mef2 allelic series to determine the gene expression profile in developing embryos at five different levels of mef2 activity. The allelic series extends from a null mutation, mef222.21, through to the control, via three hypomorphic alleles, mef2113, mef2424, and mef265. The series corresponds to different levels of Mef2 in the following order: control > 65 > 424 > 113 > 22.21. The control stock for the microarray analysis was dp cn a px sp, the stock used for the mutagenesis that produced mef265, mef2424 and mef2113. For the microarrays, 30 minute collections of control and mutant embryos for each mef2 allele were individually staged and pools of 150 embryos were then processed at mid stage 13. This corresponds to the early differentiation phase of muscle development and the expression of multiple muscle sarcomeric protein genes. Quadruplicate samples were assayed using AffymetrixÂ® Genechips by the Flychip Drosophila microarray resource.

2008-06-17 | E-GEOD-9889 | biostudies-arrayexpress

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Chromatin immunoprecipitation of Drosophila to identify muscle differentiation factor Mef2 protein binding during embryonic development

Project description:Genomewide mapping of D. melanogaster the muscle differentiation factor Mef2 protein binding during embryonic development. Five consecutive timepoints (2-4, 4-6, 6-8, 8-10, 10-12 hrs after egg-laying) were assayed in two independent repeats each. Two different antibodies were used to precipitate the Mef2 protein. Additionally the respective preimmune-serum was used as a control for every precipitation. The enriched DNA was hybridized to high density Affymetrix GeneChip Drosophila Tiling 1.0R array.

2009-11-09 | E-TABM-649 | biostudies-arrayexpress

Chromatin immunoprecipitation of Mef2 protein in Drosophila during embryonic development

Project description:Genomewide mapping of Drosophila Mef2 protein binding during embryonic development. Five consecutive timepoints (2-4, 4-6, 6-8, 8-10, 10-12 hrs after egg-laying) were assayed in four independent repeats each. Two different antibodies were used to precipitate the Mef2 protein. Additionally the respective preimmune-serum was used as a control for every precipitation. The enriched DNA was hybridized to tiling arrays covering ~ 50% of the Drosophila melanogaster genome.

2006-06-06 | E-TABM-56 | biostudies-arrayexpress

MEF2 Activated Genes

Project description:Expression profiling in hippocampal neurons to identify genes upregulated in response to ectopic MEF2 activation by MEF2-VP16-ER Experiments were conducted to identify activity-regulated MEF2 target genes. Keywords: Gene activation time course

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MEF2 Regulated Genes

Project description:Expression profiling in hippocampal neurons to identify activity-regulated genes controlled by MEF2 Experiments were conducted to identify activity-regulated MEF2 target genes. Keywords: Gene knockdown and depolarization time course

2009-01-12 | GSE13537 | GEO

Diet-MEF2 Interactions Shape Lipid Droplet Diversification in Muscle to Influence Drosophila Lifespan

Project description:The number, size, and composition of lipid droplets can be influenced by dietary changes that shift energy substrate availability. This diversification of lipid droplets can promote metabolic flexibility and shape cellular stress responses in unique tissues with distinctive metabolic roles. Using Drosophila, we uncovered a role for myocyte enhancer-factor 2 (MEF2) in modulating diet-dependent lipid droplet diversification within adult striated muscle, impacting mortality rates. Muscle-specific attenuation of MEF2, whose chronic activation maintains glucose and mitochondrial homeostasis, leads to the accumulation of large, cholesterol ester-enriched intramuscular lipid droplets in response to high calorie, carbohydrate sufficient diets. The diet-dependent accumulation of these lipid droplets also correlates with both enhanced stress protection in muscle and increases in organismal lifespan. Furthermore, MEF2 attenuation releases an antagonistic regulation of cell cycle gene expression programs, and up-regulation of Cyclin E is required for diet-and-MEF2 dependent diversification of intramuscular lipid droplets. The integration of MEF2-regulated gene expression networks with dietary responses thus plays a critical role in shaping muscle metabolism and function, further influencing organismal lifespan. Together, these results highlight a potential protective role for intramuscular lipid droplets during dietary adaptation.

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Novel targets for the transcription factors MEF2 in MA-10 Leydig cells

Project description:Testosterone production by Leydig cells is a tightly regulated process requiring synchronized expression of several steroidogenic genes by numerous transcription factors. Myocyte enhancer factor 2 (MEF2) is a transcription factor recently identified in somatic cells of the male gonad. In other tissues, MEF2 is an essential regulator of organogenesis and cell differentiation. So far in the testis, MEF2 was found to regulate Leydig cell steroidogenesis by controlling Nr4a1 and Star gene expression. To expand our understanding of the role of MEF2 in Leydig cells, we performed microarray analyses of MA-10 Leydig cells depleted in MEF2 and results were analyzed using the Partek and IPA softwares. Several genes were differentially expressed in MEF2-depleted Leydig cells and 15 were validated by qPCR. A large number of these genes are known to be involved in fertility, gonad morphology and steroidogenesis and include Pde8a, Por, Ahr, Bmal1, Cyp1a1, Cyp1b1, Map2k1, Tsc22d3, Nr0b2, Smad4, and Star, which were all downregulated in the absence of MEF2. In silico analyses revealed the presence of MEF2 binding sites within the first 2 kb upstream the transcription start site of the Por, Bmal1, and Nr0b2 promoters, which suggests a direct regulation by MEF2. Using transient transfections in MA-10 Leydig cells, siRNA knockdown, and a MEF2-Engrailed dominant negative, we found that MEF2 activates the Por, Bmal1 and Nr0b2 promoters and that this requires an intact MEF2 element. Our results identify novel target genes for MEF2 and define MEF2 as an important regulator of Leydig cell function and male reproduction.

2015-04-12 | GSE64128 | GEO

The co-existence of transcriptional activator and transcriptional repressor MEF2 complexes influences tumor aggressiveness

Project description:MEF2 (MEF2A, B, C, D) transcription factors (TFs) regulate many complex biological responses, spanning from differentiation to stress-adaptation. MEF2’s activities are therefore strictly regulated. A family of transcriptional repressors: the class IIa HDACs, which includes HDAC4, 5, 7, 9, is intimately involved in the fine tuning of MEF2 activities. In many cancer types the physiological cycle of turning on and off of MEF2 transcriptional activities is subverted due to mutations or dysregulations. On the basis of loss-of-function experiments, MEF2 factors are classified sometimes as oncogenes and sometimes as tumor suppressors. With this project we aimed to address this apparent paradox. Soft-tissue sarcomas and leiomyosarcomas (LMSs) in particular are tumors characterized by a strong repression of MEF2, which is achieved through an increase in proteasomal-mediated degradation of MEF2 proteins or in the repression exerted by HDAC4 and HDAC9. MEF2 degradation prevails in a cellular model of low-grade tumors (SK-LMS-1 cells), while in a model of high-grade LMSs (SK-UT-1 cells) MEF2 are converted into transcriptional repressors of specific genome loci. In this latter case the knock down of MEF2D and MEF2A causes the de-repression of some MEF2-target genes and, surprisingly, has a tumor suppressive effect. Our results suggest that MEF2 could provide different contributions during tumor progression in relation to the specific cellular microenvironment.

2017-04-17 | GSE94416 | GEO

The transcription factor Mef2 links the Drosophila core clock to Fas2, neuronal morphology and circadian behavior

Project description:The transcription factor Mef2 regulates activity-dependent neuronal plasticity and morphology in mammals, and clock neurons are reported to experience activity-dependent circadian remodeling in Drosophila. We show here that Mef2 is required for this daily fasciculation-defasciculation cycle. Moreover, the master circadian transcription complex CLK/CYC directly regulates Mef2 transcription. ChIP-Chip analysis identified numerous Mef2 target genes implicated in neuronal plasticity, including the cell-adhesion gene Fas2. Genetic epistasis experiments support this transcriptional regulatory hierarchy, CLK/CYC->Mef2-> Fas2, indicate that it influences the circadian fasciculation cycle within pacemaker neurons and suggest that this cycle also contributes to circadian behavior. Mef2 therefore transmits clock information to machinery involved in neuronal remodeling, which contributes to locomotor activity rhythms.

2013-05-03 | GSE46576 | GEO

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