Lysine methylation of histones is associated with both transcriptionally active chromatin and with silent chromatin, depending on what residue is modified. Histone methyltransferases and demethylases ensure that histone methylations are dynamic and can vary depending on cell cycle- or developmental stage. KDM4A demethylates H3K36me3, a modification enriched in the 3end of active genes. The genomic targets and the role of KDM4 proteins in development remain largely unknown.
Gene regulation by the lysine demethylase KDM4A in Drosophila.
No sample metadata fields
View SamplesThe Brakeless protein performs many important functions during Drosophila development, but how it controls gene expression is not understood. We previously showed that Brakeless can function as a transcriptional co-repressor. Here, we report transcriptional profiling of brakeless mutant embryos to identify additional target genes.
The Brakeless co-regulator can directly activate and repress transcription in early Drosophila embryos.
Specimen part
View SamplesThe Mediator complex is an evolutionary conserved multiprotein complex that plays an essential role in initiating and regulating transcription. Its function is to act as a universal adaptor between RNA Polymerase II and DNA-bound transcription factors to translate regulatory information from activators and repressors to the transcriptional machinery. We have found that the PFT1 gene (which encodes the MED25 subunit of the Mediator complex) is required for the uncompromised expression of both salicylic acid- and jasmonate-dependent defense genes as well as resistance to the leaf-infecting fungal pathogens, Alternaria brassicicola and Botrytis cinerea in Arabidopsis. Surprisingly, we found that the pft1/med25 mutant showed increased resistance to the root infecting pathogen Fusarium oxysporum and that this resistance was independent of classical defense genes. In addition, the over-expression of PFT1 led to increased susceptibility to F. oxysporum. Therefore, to explore this phenomenon further, we wished to use whole genome transcript profiling to identify which genes may be playing a role in pft1/med25-mediated resistance to F. oxysporum.
The mediator complex subunit PFT1 is a key regulator of jasmonate-dependent defense in Arabidopsis.
Specimen part, Treatment
View SamplesJasmonate (JA) signaling plays a key role in mediating both resistance and susceptibility to the root-infecting fungal pathogen Fusarium oxysporum. Within this system, the roles of the JA-signaling repressor gene family of JASMONATE ZIM-domain (JAZ) genes had not been investigated. By screening JAZ T DNA insertion lines for altered resistance or susceptibility to F. oxysporum, we identified a JAZ7 mutant (jaz7-1D) highly susceptible to F. oxysporum infection. Further analyses revealed jaz7-1D exhibits constitutively active JAZ7 expression, enhanced expression of JA-defense marker genes, and increased sensitivity to JA-inhibition of root elongation. To further explore altered JA-signaling and JA-responses in this mutant, we use whole transcriptome profiling of jaz7-1D versus wild-type (Col-0) plants after mock/control and JA treatment.
Characterization of a JAZ7 activation-tagged Arabidopsis mutant with increased susceptibility to the fungal pathogen Fusarium oxysporum.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of global regulators of T-helper cell lineage specification.
Specimen part
View SamplesThe aim of the dataset was to identify genome-wide regulators of gene expression in early differentiation of human cord blood derived CD4+ T cells cultured under Th1 (Act+IL12) and Th2 (Act+IL4) polarizing conditions.
Identification of global regulators of T-helper cell lineage specification.
Specimen part
View SamplesThe aim of the dataset was to identify genome-wide regulators of gene expression in early differentiation of human cord blood derived CD4+ T cells cultured under Th1 (Act+IL12) and Th2 (Act+IL4) polarizing conditions. Overall design: Total RNA from naive CD4+ T cells was compared to total RNA from cells cultured in the following three conditions: activating (antiCD3+antiCD28)+antiIL4+antiIFNG; activating (antiCD3+antiCD28)+IL12+antiIL4; activating (antiCD3+antiCD28) +IL4+antiIFNG. Samples from 3 biological replicates were analysed.
Identification of global regulators of T-helper cell lineage specification.
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View SamplesDysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream inflammatory gene synthesis in older adults remains poorly understood. Highly-purified human platelets and monocytes were isolated from healthy younger (age<45, n=37) and older (age60, n=30) adults and incubated together under autologous and non-autologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging. Basal IL-8 and MCP-1 synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous platelets, monocytes from older adults synthesized greater IL-8 (415 vs. 92 ng/mL, p<0.0001) and MCP-1 (867150 vs. 21636 ng/mL, p<0.0001) than younger adults. Non-autologous experiments demonstrated that platelets from older adults were sufficient for upregulating inflammatory gene synthesis by monocytes. Using RNA-seq followed by validation via RT-PCR and immunoblot, we discovered that granzyme A (GrmA), a serine protease not previously identified in human platelets, is increased in aging (~9-fold vs. younger adults, p<0.05) and governs increased IL-8 and MCP-1 synthesis through TLR4 and caspase-1. Inhibiting GrmA reduced the excessive IL-8 and MCP-1 synthesis in older adults to levels similar to younger adults. In summary, human aging is associated with changes in the platelet transcriptome and proteome. GrmA is present and bioactive in human platelets, is higher in older adults, and controls inflammatory gene synthesis by monocytes. Alterations in the platelet molecular signature and downstream signaling to monocytes may contribute to dysregulated inflammatory syndromes and adverse outcomes in older adults.
Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging.
Sex, Age, Specimen part, Disease
View SamplesWe have generated transgenic mice with tetracycline-regulated conditional expression of a constitutively active allele of FoxO3 under the control of the forebrain-specific CaMKIIa promoter. In adult animals, there was a reduction of brain weight by 30% and an almost complete loss of the dorsal dentate gyrus with normal cortical layering. Interestingly, the adult mice showed motor hyperactivity and a selective loss of long-term memory with normal spatial learning. We observed enhanced apoptosis starting from day E10.5. Performing microarray expression analyses and Q-PCR validation with E12.5 forebrain RNA, we observed an over-representation of thalamic markers and an under-representation of cortical markers in transgenic as compared to control animals. Immunohistochemical data show a loss of progenitors in the lateral ventricles. Up-regulation of Pik3ip1 as a target gene of FoxO3 could be responsible for the observed increase in apoptosis. The obtained forebrain expression signature is reminiscent of a Pax6 knockdown phenotype showing that expression of this FoxO3 allele during development affected neural progenitor survival and overall brain development. Conclusion: Neural progenitors are vulnerable to constitutively active FoxO3-induced apoptosis.
Expression of constitutively active FoxO3 in murine forebrain leads to a loss of neural progenitors.
Specimen part
View SamplesIn this study, we took advantage of a previously established breast cancer progression cell line model system, which consists of a parental MCF10A (MI) spontaneously immortalized mammary epithelial cell line and two of its derivatives: 1) MCF10ATk.cl2 (MII), a MCF10A H-Ras transformed cell line and 3) MCF10CA1h (MIII), derived from a xenograft of the MII cells in nude mice that progressed to carcinoma (1, 2). These cell lines were previously reported to exhibit distinct tumorigenic properties when re-implanted in nude mice; MI is non-tumorigenic, MII forms benign hyperplastic lesions and MIII forms low-grade, well differentiated carcinomas (2, 3). The advantage of this system is that these cell lines were derived from a common genetic background (MCF10A) and accumulated distinct genetic/epigenetic alterations in vivo enabling them to acquire a range of non-tumorigenic to carcinogenic properties. Our initial studies showed that MIII cells, but not MI or MII, exhibit an EMT phenotype, promoter DNA hypermethylation of epithelial genes and highly invasive properties in vitro.
Smad signaling is required to maintain epigenetic silencing during breast cancer progression.
Cell line
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