Differences in the selective pressures experienced by males and females are believed to be ubiquitous in dioecious organisms and are expected to result in the evolution of sexually antagonistic alleles, thereby driving the evolution of sexual dimorphism. Negative genetic correlation for fitness between the sexes has been documented, however, the identity, number and location of loci causing this relationship are unknown.
The sexually antagonistic genes of Drosophila melanogaster.
Specimen part
View SamplesFive different mitochondrial strains were introgressed in male and female fruit flies with identical (w1118) nuclear genetic background.
Experimental evidence supports a sex-specific selective sieve in mitochondrial genome evolution.
Sex
View SamplesIntralocus sexual conflict, where males and females have different fitness optima for the same trait, has been suggested to potentially be resolved by genomic imprinting, whereby expression in offspring is altered according to parent-of-origin. However, this idea has not yet been empirically tested. Here, we designed an experimental evolution protocol in Drosophila melanogaster which enabled us to look for imprinting effects on the X-chromosome. We enforced father-to-son transmission of the X-chromosome for many generations, and compared fitness and gene expression levels between control males, males with a control X-chromosome that had undergone one generation of father-son transmission (CDX), and males with an X-chromosome that had undergone many generations of father-son transmission (MLX). Although fitness differences were consistent with lowered fitness of males with a paternally inherited X-chromosome, expression differences suggested that this was due to deleterious maternal effects rather than imprinting. We conclude that imprinting is unlikely to resolve intralocus sexual conflict in Drosophila melanogaster.
Epigenetics and sex-specific fitness: an experimental test using male-limited evolution in Drosophila melanogaster.
Sex, Specimen part, Treatment
View SamplesBackground The evolution of female choice mechanisms favouring males of their own kind is considered as crucial step during the early stages of speciation. However, although the genomics of mate choice may influence both the likelihood and speed of speciation, the identity and location of genes underlying assortative mating remain largely unknown.
Female Drosophila melanogaster gene expression and mate choice: the X chromosome harbours candidate genes underlying sexual isolation.
Age, Specimen part, Treatment
View SamplesOne clear hallmark of mammalian promoters is the presence of CpG islands (CGIs) at more than two thirds of genes whereas TATA boxes are only present at a minority of promoters. Using genome-wide approaches, we show that GC content and CGIs are major promoter elements in mammalian cells, able to govern open chromatin conformation and support paused transcription. First, we define three classes of promoters with distinct transcriptional directionality and pausing properties which correlate with their GC content. We further analyze the direct influence of GC content on nucleosome positioning and depletion, and show that CGIs correlate with nucleosome depletion both in vivo and in vitro. We also show that transcription is not essential for nucleosome exclusion but influences both a weak +1 and a well-positioned nucleosome at CGI borders. Altogether our data support the idea that CGIs have become an essential feature of promoter structure defining novel regulatory properties in mammals. Overall design: Nucleosome density and positioning were studied by high-throughput sequencing of DNA previously treated with Mnase. In parallel, chIPseq for PolII and H3K27ac were performed in mouse and human with different conditions to assess a potential effect of transcription on nucleosomes properties. To investigate transcription at promoters, we analyzed together with genome-wide Pol II accumulation by ChIP-Seq, paused bidirectional transcripts associated with transcription start sites (TSS RNAs).
CpG islands and GC content dictate nucleosome depletion in a transcription-independent manner at mammalian promoters.
Specimen part, Cell line, Subject
View SamplesArp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis.We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistently, we unveiled that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocytes'' shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis. Overall design: Gene expression profile of wt and ARPC4 ko epidermis
Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2.
Specimen part, Cell line, Subject
View SamplesArp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis.We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistently, we unveiled that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocytes'' shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis. Overall design: Gene expression profile of wt, ARPC4 ko and EGFP-Nrf2 expressing keratinocytes.
Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2.
Specimen part, Cell line, Subject
View SamplesTranscriptomic response to metfromin treatment.
Genomic Characterization of Metformin Hepatic Response.
Sex, Age, Specimen part, Cell line
View Samples15-25% of breast cancers (BC) show ERBB2-amplification and overexpression of the encoded ERBB2 tyrosine kinase receptor. They are associated with a poor prognosis but can benefit from targeted therapy. A better knowledge of these BCs may help understand their behavior and design new therapeutic strategies. In this study, we defined the high resolution genome and gene expression profiles of 54 ERBB2-amplified BCs using 244K oligonucleotide array-comparative genomic hybridization and whole-genome DNA microarrays. We first identified the ERBB2-C17orf37-GRB7 genomic segment as the minimal common amplicon, and CRKRS and IKZF3 as the most frequent centromeric and telomeric amplicon borders, respectively. Second, we identified 17 genome regions affected by copy number aberration (CNA). The expression of 37 genes of these regions was deregulated. Third, two types of heterogeneity were observed in ERBB2-amplified BCs. The genomic profiles of estrogen receptor-postive (ER+) and negative (ER-) ERBB2-amplified BCs were different. The WNT/-catenin signaling pathway was involved in ER- ERBB2-amplified BCs, and PVT1 and TRPS1 were candidate oncogenes associated with ER+ ERBB2-amplified BCs. The size of the ERBB2-amplicon was different in inflammatory (IBC) and non inflammatory BCs. ERBB2-amplified IBCs were characterized by the downregulated and upregulated mRNA expression of ten and two genes in proportion to CNA, respectively. We have shown that ERBB2 BCs are heterogeneous and identified genomic features that may be useful in the design of therapeutical strategies
Genome profiling of ERBB2-amplified breast cancers.
No sample metadata fields
View SamplesThe edr1 mutant of Arabidopsis thaliana displays enhanced resistance to the powdery mildew Golovinomyces cichoracearum, resulting in cell death and an absence of visible disease symptoms. To better characterize and understand the defense response of edr1, a time course of early signaling responses was performed after inoculation with powdery mildew and compared to the responses of wild-type Col-0. These time points represent early stages in the infection process, before any signs of susceptibility or resistance are visible.
Negative regulation of defence signalling pathways by the EDR1 protein kinase.
No sample metadata fields
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