Identification of a NVS-ZP7-3 response signature in T-ALL cell lines to understand the transcriptional response in both Notch pathway active cell lines and Notch pathway inactive lines.
Discovery of a ZIP7 inhibitor from a Notch pathway screen.
Cell line, Treatment
View SamplesGene expression analysis is a widely used and powerful method for investigating the transcriptional behavior of biological systems, for classifying cell states in disease and for many other purposes. Recent studies indicate that common assumptions currently embedded in experimental and analytical practices can lead to misinterpretation of global gene expression data. We discuss these assumptions and describe solutions that should minimize erroneous interpretation of gene expression data from multiple analysis platforms. Overall design: Polyadenylated RNA depleted of ribosomal content was used for preparation of two independent sequencing libraries (low-Myc & high-Myc). A panel of synthetic RNA''s was added to these populations, based on cell number.
Revisiting global gene expression analysis.
Specimen part, Cell line, Subject
View SamplesTranscription factors (TFs) bind specific sequences in promoter-proximal and distal DNA elements in order to regulate gene transcription. RNA is transcribed from both promoter-proximal and distal DNA elements, and some DNA-binding TFs have also been shown to bind RNA. These obsevations led us to postulate that RNA transcribed from regulatory elements contributes to stable TF occupancy at these regulatory elements. We show here that the ubiquitously expressed TF YY1 binds to both proximal and distal regulatory elements and to the RNA species associated with these elements near active genes in embryonic stem cells. Inhibition of transcription from these elements reduces YY1 occupancy. In contrast, tethering of RNA species near YY1 DNA binding sites enhances YY1 occupancy. We propose that RNA acts as trap to maintain certain TFs at active enhancer and promoter-proximal regulatory elements. Thus, transcriptional control generally involves a positive feedback loop, where YY1 and other TFs stimulate local transcription, and newly transcribed nascent RNA reinforces local TF occupancy. This model helps explain why TFs occupy only the small fraction of their consensus motifs in the mammalian genome where transcription is detected. Overall design: RNA-Seq in mouse embryonic stem cells before and after knockdown of exosome protein
Transcription factor trapping by RNA in gene regulatory elements.
Specimen part, Subject
View SamplesA remarkable number of long non-coding RNA (lncRNA) species have been identified in mammalian cells, but the genomic origins of these molecules in individual cell types is poorly understood. As a prerequisite to studying the transcriptional regulation of lncRNAs, we conducted a comprehensive analysis of the genomic origins of lncRNAs expressed in embryonic stem cells (ESCs). Overall design: Polyadenylated RNA and total RNA depleted of ribosomal content was used for preparation of two independent sequencing libraries
Divergent transcription of long noncoding RNA/mRNA gene pairs in embryonic stem cells.
Specimen part, Cell line, Subject
View SamplesThere is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not depend on this structural protein. Here we show that the transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF. YY1 binds to active enhancers and promoter-proximal elements in all cells examined. YY1 forms dimers that can facilitate DNA interactions. Deletion of YY1 binding sites or depletion of YY1 can disrupt enhancer-promoter looping and normal gene expression. We propose that YY1-mediated enhancer-promoter interactions are a general feature of mammalian gene control. Overall design: Single-end 40 bp Poly-A RNA-seq in mouse embryonic stem cells before and after YY1 depletion
YY1 Is a Structural Regulator of Enhancer-Promoter Loops.
Specimen part, Treatment, Subject, Time
View SamplesThere is considerable evidence that chromosome structure plays important roles in gene control, but we have limited understanding of the proteins that contribute to structural interactions between gene promoters and their enhancer elements. Large DNA loops that encompass genes and their regulatory elements depend on CTCF-CTCF interactions, but most enhancer-promoter interactions do not depend on this structural protein. Here we show that the transcription factor Yin Yang 1 (YY1) contributes to enhancer-promoter structural interactions in a manner analogous to DNA interactions mediated by CTCF. YY1 binds to active enhancers and promoter-proximal elements in all cells examined. YY1 forms dimers that can facilitate DNA interactions. Deletion of YY1 binding sites or depletion of YY1 can disrupt enhancer-promoter looping and normal gene expression. We propose that YY1-mediated enhancer-promoter interactions are a general feature of mammalian gene control. Overall design: Single-cell RNA-seq in mouse embryonic stem cells with and without YY1 protein
YY1 Is a Structural Regulator of Enhancer-Promoter Loops.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.
Specimen part
View SamplesAn investigation of the global gene expression signatures of murine hematopoietic stem cell differentiation during steady state hematopoiesis.
Epigenetic chromatin states uniquely define the developmental plasticity of murine hematopoietic stem cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dominant negative PPARγ promotes atherosclerosis, vascular dysfunction, and hypertension through distinct effects in endothelium and vascular muscle.
Specimen part
View SamplesPharmacological activation of the transcription factor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. In contrast, naturally occurring mutations (e.g., P467L, V290M) in the ligand binding domain of PPAR gamma in humans leads to severe insulin resistance and early-onset hypertension. Experimental evidence, including whole genome expression profiling, suggests that these mutant versions of PPAR gamma act in a dominant negative manner. Because PPAR gamma is expressed in a variety of cell types and tissues, we generated a transgenic mouse model (SP467L) specifically targeting dominant negative PPAR gamma to the vascular smooth muscle cells in order to determine the action of PPAR gamma in the blood vessel independent of its systemic metabolic actions. In the data set provided herein, we examined the gene expression profile in thoracic aorta from SP467L mice and their control littermates using the Affymetrix Mouse Genome 430 2.0 array.
Dominant negative PPARγ promotes atherosclerosis, vascular dysfunction, and hypertension through distinct effects in endothelium and vascular muscle.
Specimen part
View Samples