Transcription is a multi-stage process that coordinates several steps within the transcription cycle including chromatin reorganization, RNA polymerase II recruitment, initiation, promoter clearance and elongation. Recent advances have identified the super elongation complex (SEC), containing the eleven nineteen lysine rich leukemia protein (ELL), as a key regulator of transcriptional elongation. We show here that ELL plays a diverse and kinetically distinct role prior to its assembly into the SEC by stabilizing Pol II recruitment/initiation and entry into the pause site. Loss of ELL destabilizes the PIC complexes and results in disruption of early elongation and promoter proximal chromatin structure prior to recruitment of AFF4 and other SEC components. These changes result in significantly reduced transcriptional activation of rapidly induced genes. Thus, ELL plays an early and essential role during rapid high amplitude gene expression that is required for both Pol II pause site entry and release.
ELL facilitates RNA polymerase II pause site entry and release.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.
Sex, Specimen part
View SamplesPreimplantation embryos undergo a transient wave of genome-wide demethylation with the exception of imprinted genes that are critical for fetal development. Here we show that the derivation of female mouse embryonic stem cells (ESCs) in the presence of inhibitors of MEK1/2 and Gsk3 (2i-ESCs), known as 2i or ground-state culture conditions, results in a widespread loss of DNA methylation including a massive erasure of genomic imprints. In this study, we analyzed global gene expression profile and global DNA methylation status in 2i-ESCs and 2i-ESCs derived differentiated cells. S-ESCs are ESCs established under serum-containing medium. 2i_S_ESCs are ESCs established in 2i-containing medium, followed by maintenance in serum-containing medium.
Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.
Specimen part
View SamplesTo identify downstream transcription factors induced by retinoic acid, we stimulated SFZ cells with 10 M retinoic acid for 24 hours and performed microarray analysis.
Sox4 is involved in osteoarthritic cartilage deterioration through induction of ADAMTS4 and ADAMTS5.
Specimen part, Treatment
View SamplesNeural stem cells (NSC) with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat spinal cord injury, stroke, and neurodegenerative diseases. To efficiently induce neuronal lineage cells from NSC for neuron replacement therapy, we should clarify the intrinsic genetic programs involved in a time and place-specific regulation of human NSC differentiation. Recently, we established an immortalized human NSC clone HB1.F3 to provide an unlimited NSC source applicable to genetic manipulation for cell-based therapy. To investigate a role of neurogenin 1 (Ngn1), a proneural basic helix-loop-helix (bHLH) transcription factor, in human NSC differentiation, we established a clone derived from F3 stably overexpressing Ngn1. Genome-wide gene expression profiling identified 250 upregulated genes and 338 downregulated genes in Ngn1-overexpressing F3 cells (F3-Ngn1) versus wild-type F3 cells (F3-WT). Notably, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a novel stem cell marker, showed a robust increase in F3-Ngn1.
Stable expression of neurogenin 1 induces LGR5, a novel stem cell marker, in an immortalized human neural stem cell line HB1.F3.
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View SamplesAssisted reproductive technologies, including in vitro fertilization (IVF), are now frequently used, and increasing evidence indicates that IVF causes gene expression changes in children and adolescents that increase the risk of metabolic diseases. Although such gene expression changes are thought to be due to IVF-induced epigenetic changes, the mechanism remains elusive.
The transcription factor ATF7 mediates <i>in vitro</i> fertilization-induced gene expression changes in mouse liver.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer.
Specimen part, Cell line, Treatment
View SamplesCtBP is a global co-repressor by serving as transcriptional factor in multiple pathways. CtBP functioned as transcriptional factor by recruiting other cofactors such as G9a, HDAC1 and PcG proteins. CtBP is found to be over enriched in several type of tumor samples. To dipict the role of CtBP in globally regulating gene expression, we applied gene microarray technology to find out what subgroups of genes are mainly affected.
Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer.
Cell line, Treatment
View SamplesCo-stimulatory molecules of the CD28 family on T lymphocytes integrate cues from innate immune system sensors, and modulate activation responses in conventional CD4+ T cells (Tconv) and their FoxP3+ regulatory counterparts (Treg). To better understand how costimulatory and co-inhibitory signals might be integrated, we profiled the changes in gene expression elicited in the hours and days after engagement of Treg and Tconv by anti-CD3 and either anti-CD28, -CTLA4, -ICOS, -PD1, -BTLA or -CD80.
Convergent and divergent effects of costimulatory molecules in conventional and regulatory CD4+ T cells.
Sex, Age, Specimen part
View SamplesA comparative analysis of gene expression of CD4+ EGFP+ Nrp1+ (tTreg, thymus-derived Treg), CD4+ EGFP+ Nrp1- (pTreg, peripherally-derived Treg) and CD4+ EGFP- (Tconv, conventional T cell) in CD28-/- Foxp3EGFP and Foxp3EGFP mice. Overall design: Nrp1+ Treg (tTreg), Nrp1- Treg (pTreg) and Tconv were sorted from Foxp3EGFP and CD28-/-Foxp3EGFP mice. Total RNAs were extracted from whole samples and analyzed by RNA-seq.
CD28 co-stimulation is dispensable for the steady state homeostasis of intestinal regulatory T cells.
Specimen part, Cell line, Subject
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