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SRP074463
Mus musculus
40 Downloadable Samples
Illumina HiSeq 2500
Description
We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations. Overall design: GMP and MEP were isolated from Runx1+/+-Tg(vav-Cre) and Runx1fl/fl-Tg(vav-Cre) mice as well as Runx1fl/fl-Tg(vav-Cre) XMP, total RNA extracted and sequenced
Publication Title
Runx1 downregulates stem cell and megakaryocytic transcription programs that support niche interactions.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms by which downstream programs are activated are incompletely understood. The preB-cell receptor (preBCR) is an important checkpoint of B-cell development and essential for a preB-cell to traverse into an immature B-cell. Here, we show that activation of Mef2 transcription factors by preBCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the preB-cell stage in mice deficient for Mef2c and Mef2d transcription factors and that preBCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the ERK5 mitogen activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development. Overall design: RNA-seq experiments were performed from Mef2c/d knockout proB-cells versus control cells to identify genes regulated by Klf2
Publication Title
Essential control of early B-cell development by Mef2 transcription factors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms by which downstream programs are activated are incompletely understood. The preB-cell receptor (preBCR) is an important checkpoint of B-cell development and essential for a preB-cell to traverse into an immature B-cell. Here, we show that activation of Mef2 transcription factors by preBCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the preB-cell stage in mice deficient for Mef2c and Mef2d transcription factors and that preBCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the ERK5 mitogen activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development. Overall design: RNA-seq experiments were performed from Blnk-/- preB-cells with an integration of BLNK-ERt2 to identify genes regulated after preBCR signaling
Publication Title
Essential control of early B-cell development by Mef2 transcription factors.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms by which downstream programs are activated are incompletely understood. The preB-cell receptor (preBCR) is an important checkpoint of B-cell development and essential for a preB-cell to traverse into an immature B-cell. Here, we show that activation of Mef2 transcription factors by preBCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the preB-cell stage in mice deficient for Mef2c and Mef2d transcription factors and that preBCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the ERK5 mitogen activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development. Overall design: RNA-seq experiments were performed from Klf2 overexpressing BMiFLT3 (15-3) cells to identify genes regulated by Klf2
Publication Title
Essential control of early B-cell development by Mef2 transcription factors.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms by which downstream programs are activated are incompletely understood. The preB-cell receptor (preBCR) is an important checkpoint of B-cell development and essential for a preB-cell to traverse into an immature B-cell. Here, we show that activation of Mef2 transcription factors by preBCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the preB-cell stage in mice deficient for Mef2c and Mef2d transcription factors and that preBCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the ERK5 mitogen activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development. Overall design: RNA-seq experiments were performed from Klf2 knockout proB-cells versus control cells to identify genes regulated by Klf2
Publication Title
Essential control of early B-cell development by Mef2 transcription factors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
The estrogen receptor-a (ERa) is a transcription factor which plays a critical role in controlling cell proliferation and tumorigenesis by recruiting various cofactors to estrogen response elements (EREs) to induce or repress gene transcription. A deeper understanding of these transcriptional mechanisms may uncover novel therapeutic targets for ERa-dependent cancers. Here we show for the first time that BRD4 regulates ERa-induced gene expression by affecting elongation-associated phosphorylation of RNA Polymerase II (RNAPII P-Ser2) and histone H2B monoubiquitination (H2Bub1). Consistently, BRD4 activity is required for estrogen-induced proliferation of ER+ breast and endometrial cancer cells and uterine growth in mice. Genome-wide occupancy studies revealed an enrichment of BRD4 on transcriptional start sites as well as EREs enriched for H3K27ac and demonstrate a requirement for BRD4 for H2B monoubiquitination in the transcribed region of estrogen-responsive genes. Importantly, we further demonstrate that BRD4 occupancy correlates with active mRNA transcription and is required for the production of ERa-dependent enhancer RNAs (eRNAs). These results uncover BRD4 as a central regulator of ERa function and potential therapeutic target. Overall design: mRNA expression profiles of MCF7 cells treated with +/- estrogen treatment under negative control siRNA, BRD4 siRNA or JQ1 treatment, in duplicates.
Publication Title
Bromodomain protein BRD4 is required for estrogen receptor-dependent enhancer activation and gene transcription.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
We synthesized the PAX8-NFE2L2 fusion transcript and cloned it into a lentiviral vector, and used this to overexpress it in the murine prostate adenocarcinoma cell line TRAMP-C1. Overall design: We used high coverage RNA sequencing (>30 million reads per sample) to compare the expression profiles of cells expressing the PAX8-NFE2L2 fusion transcript to cells transduced with an empty vector.
Publication Title
Global analysis of somatic structural genomic alterations and their impact on gene expression in diverse human cancers.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Bromodomain-containing protein 4 (BRD4) is an important epigenetic reader which promotes gene transcription to modulate cell-specific functions and is under intensive investigation for its potential as an anti-tumor therapeutic target. However, the role of BRD4 in non-transformed cells remains unclear. Here we demonstrate that BRD4 is required for the expression of epithelial-specific genes and suppression of stem cell-like properties by binding to the distal regions of epithelial-related genes. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription of epithelial differentiation-specific genes. Interestingly, we show that BRD4 perturbation regulates the expression of Grainy Head-like transcription factor, GRHL3, whose depletion partially mimics BRD4 inhibition and blocks differentiated phenotype. By binding to the distal regions of GRHL3, BRD4 promotes RNA polymerase-II occupancy and thus affects eRNA transcription. Altogether, these findings provide evidence that BRD4 promotes a differentiated epithelial phenotype in non-transformed mammary cells at least in part through the activation of GRHL3 expression. Overall design: mRNA expression profiles of MCF10A cells under negative control siRNA, BRD4 siRNA or JQ1 treatment, in duplicates.
Publication Title
BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
Expression analysis of genes potentially regulated by BMPRII and beta-catenin. BMPRII has been linked as a genetic factor to the disease pulmonary arterial hypertension.
Publication Title
Disruption of PPARγ/β-catenin-mediated regulation of apelin impairs BMP-induced mouse and human pulmonary arterial EC survival.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- IlluminaHiSeq2000
Description
Some of the functions and mechanisms of PPAR?-mediated regulation of vascular homeostasis have been revealed, the potential role of PPAR? in angiogenesis is obscure. In human ECs, PPAR?-deficiency was studied using siRNA strategy and RNA sequencing was utilized to reveal angiogenesis-associated targets for PPARg. Overall design: Our aim is to reveal the possible role of PPARy in angiogenesis.
Publication Title
Loss of PPARγ in endothelial cells leads to impaired angiogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples