Transcript profile of apices of 20 days-old Arabidopsis plants over expressing miR396b.
Repression of cell proliferation by miR319-regulated TCP4.
Age, Specimen part
View SamplesTranscript profile of 10 days-old seedlings over expressing miR396
Control of cell proliferation in Arabidopsis thaliana by microRNA miR396.
No sample metadata fields
View SamplesThe Growth Regulating Factors (GRFs) are plant specific transcription factors. They form complexes with GRF Interacting Factors (GIFs), a small family of transcriptional co-activators. In Arabidopsis thaliana, seven out of the nine GRFs are regulated by microRNA miR396. A detailed analysis of GRF3 revealed that a modified transgene, insensitive to the regulation of miR396, causes a strong increase in the number of cells in leaves, while an additional increase of GIF1 expression further enhances the number of cells synergistically. Genome-wide transcript profiling revealed that simultaneous increase of GRF3 and GIF1 levels causes additional effects in gene expression compared to either of the transgenes alone. We observed that GIF1 interacts in vivo with GRF3, as well as chromatin remodeling complexes, providing a mechanistic explanation for the additional activities of a GRF3-GIF1 complex. Interestingly, we found that the GRF system also regulates leaf longevity. Genetic and molecular analysis revealed that the functions of GRFs in leaf size and senescence can be uncoupled, demonstrating that the GRFs control different stages of leaf development. The results provide new insights into the functions of a complex regulatory network composed of microRNAs, transcription factors, and co-transcription factors.
Post-transcriptional control of GRF transcription factors by microRNA miR396 and GIF co-activator affects leaf size and longevity.
Specimen part
View SamplesAnalysis of gene expression in the meristematic zone of Arabidopsis roots overexpressing miR396
MicroRNA miR396 Regulates the Switch between Stem Cells and Transit-Amplifying Cells in Arabidopsis Roots.
Age, Specimen part
View SamplesAnalysis of transcriptomic fidelity between primary and pdx tumor. The hypothesis tested in the present study was that pdx can serve as high fidelity models of human cancer and guide longitudinal care. Results provide important information on the response of preservation of gene expression changes between the primary tumor and the first generation pdx.
Case study: patient-derived clear cell adenocarcinoma xenograft model longitudinally predicts treatment response.
No sample metadata fields
View SamplesAn unexplored consequence of epigenetic alterations associated with cancer is the ectopic expression of tissue-restricted genes. Here, a new strategy was developed to decipher genome-wide expression data in search for these off-context gene activations, which consisted first, in identifying a large number of tissue-specific genes normally epigenetically silenced in most somatic cells and second, in using them as cancer biomarkers on an on/off basis. Applying this concept to analyze whole-genome transcriptome data in lung cancer, we discovered a specific group of 26 genes whose expression was a strong and independent predictor of poor prognosis in our cohort of 293 lung tumours, as well as in two independent external populations. In addition, these 26 classifying genes enabled us to isolate a homogenous group of metastatic-prone highly aggressive tumours, whose characteristic gene expression profile revealed a high proliferative potential combined to a significant decrease in immune and signaling functions. This work illustrates a new approach for a personalized management of cancer, with applications to any cancer type.
Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.
Sex, Specimen part
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Bromodomain-dependent stage-specific male genome programming by Brdt.
Specimen part
View SamplesMale germ cell differentiation is a highly regulated multistep process initiated by the commitment of progenitor cells into meiosis and characterized by major chromatin reorganizations in haploid spermatids. We report here that a single member of the double bromodomain BET factors, Brdt, is a master regulator of both meiotic divisions and post-meiotic genome repackaging. Upon its activation at the onset of meiosis, Brdt drives and determines the developmental timing of a testis-specific gene expression program. In meiotic cells, Brdt initiates a genuine histone acetylation-guided programming of the genome by activating essential meiotic genes and repressing a progenitor cells gene expression program, while priming a post-meiotic gene group for further activation. At post-meiotic stages, a global chromatin hyperacetylation gives the signal for Brdts first bromodomain to direct the genome-wide replacement of histones by transition proteins. Brdt is therefore a unique and essential regulator of male germ cell differentiation, which, by using various domains in a developmentally controlled manner, first drives a specific spermatogenic gene expression program, and later controls the tight packaging of the male genome.
Bromodomain-dependent stage-specific male genome programming by Brdt.
No sample metadata fields
View SamplesImmuno-chemotherapy regimens elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumors in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that drives aggressive tumor growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma.
Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Specimen part
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