We previously generated genetically engineered mouse (GEM) models based on perturbation of Tp53, Rb with or without Brca1 or Brca2 that develop serous epithelial ovarian cancer (SEOC) closely resembling the human disease on histologic and molecular levels. We have adapted these GEM models to orthotopic allografts that uniformly develop tumors with short latency in immunocompetent recipients and are ideally suited for routine preclinical studies. To monitor passaged tumors at the molecular level, we analyzed transcriptional profiles of a set of primary SEOC and matching derived passaged tumors. We have merged this dataset with previously published ( doi: 10.1158/0008-5472.CAN-11-3834; PMID 22617326) dataset of murine primary ovarian tumors from our GEM models (GSE46169) and merged and compared them to expression profiles of human dataset published previously (doi: 10.1038/nature10166).
Pathway-specific engineered mouse allograft models functionally recapitulate human serous epithelial ovarian cancer.
Specimen part
View SamplesUnderstanding how the expression of transcription factor (TF) genes is modulated is essential for reconstructing gene regulatory networks. There is increasing evidence that sequences other than upstream noncoding can contribute to modulating gene expression, but how frequently they do so remains unclear. Here, we investigated the regulation of TFs expressed in a tissue-enriched manner in Arabidopsis roots. For 61 TFs, we created GFP reporter constructs driven by each TF's upstream noncoding sequence (including the 5'UTR) fused to the GFP reporter gene alone or together with the TF's coding sequence. We compared the visually detectable GFP patterns with endogenous mRNA expression patterns, as defined by a genome-wide microarray root expression map.
Transcriptional and posttranscriptional regulation of transcription factor expression in Arabidopsis roots.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global target mRNA specification and regulation by the RNA-binding protein ZFP36.
Cell line, Treatment
View SamplesTristetraprolin/ZFP36/TTP and ELAVL1/HuR are two disease-relevant RNA-binding proteins (RBPs) that both interact with AU-rich sequences but have antagonistic roles. While ELAVL1 binding has been profiled in several studies, the precise in vivo binding specificity of ZFP36 has not been investigated on a global scale. We determined ZFP36 binding preferences using cross-linking and immunoprecipitation in human embyonic kidney cells and examined combinatorial regulation of AU-rich elements by ZFP36 and ELAVL1. Among the targets ZFP36 binds and negatively regulates the mRNA of genes encoding proteins necessary for immune function and cancer, and other RBPs. Using partial correlation analysis, we were able to quantify the association between ZFP36 binding sites and differential target RNA abundance from ZFP36 overexpression independent of effects from confounding features, such as 3 UTR length. We identified thousands of overlapping ZFP36 and ELAVL1 binding sites, in 1,313 genes. ZFP36 preferentially interacts with and regulates AU-rich sequences while ELAVL1 prefers predominantly U- and CU-rich sequences. RNA target specificity identified by global in vivo ZFP36-mRNA interactions were quantitatively similar to previously reported in vitro binding affinities. ZFP36 and ELAVL1 both bind an overlapping spectrum of RNA sequences, yet with differential relative preferences that dictate combinatorial regulatory potential. Our findings and methodology delineate an approach to untangle the in vivo combinatorial regulation by RNA-binding proteins.
Global target mRNA specification and regulation by the RNA-binding protein ZFP36.
Cell line, Treatment
View SamplesTranscriptional programs that regulate development are exquisitely controlled in space and time. Elucidating these programs that underlie development is essential to understanding the acquisition of cell and tissue identity. We present microarray expression profiles of a high resolution set of developmental time points within a single Arabidopsis root, and a comprehensive map of nearly all root cell-types. These cell-type specific transcriptional signatures often predict novel cellular functions. A computational pipeline identified dominant expression patterns that demonstrate transcriptional connections between disparate cell types. Dominant expression patterns along the roots longitudinal axis do not strictly correlate with previously defined developmental zones, and in many cases, expression fluctuation along this axis was observed. Both robust co-regulation of gene expression and potential phasing of gene expression were identified between individual roots. Methods that combine these two sets of profiles demonstrate transcriptionally rich and complex programs that define Arabidopsis root development in both space and time.
A high-resolution root spatiotemporal map reveals dominant expression patterns.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.
Specimen part
View SamplesIntegrative regulatory mapping indicates that the RNA-binding protein HuR (ELAVL1) couples pre-mRNA processing and mRNA stability
Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.
Specimen part
View SamplesDivergent transcription, in which reverse-oriented transcripts occur upstream of eukaryotic promoters in regions devoid of annotated genes, has been suggested to be a general property of active promoters. Here we show that the human basal RNA polymerase II transcriptional machinery and core promoter are inherently unidirectional, and that reverse-oriented transcripts originate from their own cognate reverse-directed core promoters. In vitro transcription analysis and mapping of nascent transcripts in cells revealed that core promoters are unidirectional and that sequences at reverse start sites are similar to those of their forward counterparts. The use of DNase I accessibility to define proximal promoter borders revealed that about half of promoters are unidirectional and that these unidirectional promoters are depleted at their upstream edges of reverse core promoter sequences and their associated chromatin features. Divergent transcription is thus not an inherent property of the transcription process, but rather the consequence of the presence of both forward- and reverse-directed core promoters. Overall design: Using 5''-GRO-seq and GRO-seq to determine mechanisms of divergent transcription initiation
Human promoters are intrinsically directional.
No sample metadata fields
View SamplesIL-2 production defines precursors fated to become T Follicular Helper cells Overall design: Sorted naïve IL-2.eGFP CD4 T cells were activvated in vitro or in vivo. Total RNA was isolated from CD69+ IL-2.eGFP+ and CD69+ IL-2.eGFP– CD4 T cells 18-24 hours after activation.
Differential IL-2 expression defines developmental fates of follicular versus nonfollicular helper T cells.
Specimen part, Cell line, Subject
View SamplesWe sorted for GFP+ cells using the enhancer trap J0571 with the UAS promoter driving the expression of different BIRD genes. Different genetic backgrounds are use and listed below.
Transcriptional control of tissue formation throughout root development.
Specimen part
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