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GSE109284
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DC), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migration in vitro and in vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished LXR-dependent induction of DC chemotaxis. Using the LDLR-/- mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for efficient emigration of DCs in response to chemotactic signals during inflammation.
Publication Title
LXR nuclear receptors are transcriptional regulators of dendritic cell chemotaxis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mouse BMDCs were differentiated from bone marrow by GM-CSF and IL-4 for 9 days.
Publication Title
LXR nuclear receptors are transcriptional regulators of dendritic cell chemotaxis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 44 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The role of Striatin Interacting Protein 2 (Strip2) in differentiation of embryonic stem cells (ESCs) is still under debate. Strip2 silenced (KD) ESCs were differentiated for 4, 8, 12, and 16 days. We show that Strip2 is distributed in the perinucleus or nuclei of wild type (WT) undifferentiated ESCs, but is localized in high-density nuclear bodies in differentiated cells. CellNet analysis of microarray gene expression data for KD and scrambled control (SCR) embryoid bodies (EBs), as well as immunostainings of key pluripotent factors, demonstrated that KD ESCs remain undifferentiated. This occurs even in 16-day old EBs, which possessed a high tumorigenic potential. Correlated with very high expression levels of epigenetic regulator genes, Hat1 and Dnmt3, enzymatic activities of the histone acetyltransferase type B (HAT1) and DNA (cytosine-5)-methyltransferase 3 beta (DNMT3b) were higher in differentiated 16-day old KD EBs than in SCR or WT EBs. The expression levels of let-7, 290 and 302 microRNA families were opposed in KD ESCs, while KD EBs had levels comparable to WT and SCR ESCs during differentiation. This demonstrates that Strip2 is critical to the onset of differentiation, regulating expression of epigenetic regulators, HAT1 and DNMT3b, as well as microRNAs involved in pluripotency.
Publication Title
STRIP2 Is Indispensable for the Onset of Embryonic Stem Cell Differentiation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Caenorhabditis elegans
- 18 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Analysis of wildtype (N2) C. elegans fed different diets: E. coli OP50, E. coli HT115 and Comamonas DA1877
Publication Title
Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Analysis of wildtype (N2) C. elegans fed different diets: E. coli OP50, Comamonas DA1877, and Diluted Comamonas (1:1000 Comamonas DA1877:E. coli OP50)
Publication Title
Diet-induced developmental acceleration independent of TOR and insulin in C. elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 25 Downloadable Samples
Illumina HiSeq 2500
Description
Polycomb repressive complex 2 (PRC2-EZH2) methylates histone H3 at lysine 27 (H3K27) and is required to maintain gene repression during development. Misregulation of PRC2 is linked to a range of neoplastic malignancies, which is believed to involve methylation of H3K27. However, the full spectrum of non-histone substrates of PRC2 that might also contribute to PRC2 function is not known. We characterized the target recognition specificity of PRC2 and used the resultant data to screen for novel potential targets. The RNA polymerase II (Pol II) transcription factor, Elongin A (EloA), is methylated by PRC2 in vivo. Mutation of the methylated EloA residue decreased repression of many, but not all, PRC2 target genes as measured by both steady state and nascent RNA levels. We propose that PRC2 regulates transcription of a subset of target genes in part via methylation of EloA. Overall design: We examined the transcripitonal profile of EEDnull, EloAnull, EloA mutant, and parental mouse embryonic stem cells by RNAseq. Please note that the .bw processed data file was generated from the *mESC replicate samples together and linked to the corresponding *rep1 sample records.
Publication Title
Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Polycomb repressive complex 2 (PRC2-EZH2) methylates histone H3 at lysine 27 (H3K27) and is required to maintain gene repression during development. Misregulation of PRC2 is linked to a range of neoplastic malignancies, which is believed to involve methylation of H3K27. However, the full spectrum of non-histone substrates of PRC2 that might also contribute to PRC2 function is not known. We characterized the target recognition specificity of PRC2 and used the resultant data to screen for novel potential targets. The RNA polymerase II (Pol II) transcription factor, Elongin A (EloA), is methylated by PRC2 in vivo. Mutation of the methylated EloA residue decreased repression of many, but not all, PRC2 target genes as measured by both steady state and nascent RNA levels. We propose that PRC2 regulates transcription of a subset of target genes in part via methylation of EloA. Overall design: We examined the nascent transcripiton profile of mES cells by adding 5-Bromouridine (BrU) to the media for 10 min. Following RNA isolation, BrU-labelled nascent RNA species were affinity purified using BrdU antibody and sequenced after library preparation. Please note that each .bw file was generated from two replicate samples together and linked to the corresponding *rep1 sample records.
Publication Title
Polycomb Repressive Complex 2 Methylates Elongin A to Regulate Transcription.
Sample Metadata Fields
Specimen part, Subject
View Samples- Caenorhabditis elegans
- 9 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Analysis of wildtype C. elegans (N2) and pcca-1(ok2282) and metr-1(ok521) mutants fed Comamonas DA1877
Publication Title
Integration of metabolic and gene regulatory networks modulates the C. elegans dietary response.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The analysis of several mammalian genomes has revealed between 20,000 to 30,000 genes in each genome, a number that may seem hard to reconcile with the large number of cell types and complex functions of these organisms. The solution to this paradox partly lies in the large array of transcripts that each gene can potentially generate through usage of alternative promoters and the variable levels of transcripts that each gene produces in different tissues and cell types. Thus, in order to understand the mechanisms that control diverse patterns of gene expression in mammals, it is necessary to accurately define the active promoters and monitor their cell or tissue-dependent activity. Previous high throughput strategies for assaying tissue-specific gene expression have primarily relied on measurements of steady-state transcript levels by microarrays or tag sequencing. Here, we employ a new experimental strategy to identify and characterize tissue specific promoters by integrating genome-wide maps of RNA polymerase II (Pol II) binding, chromatin modifications and gene expression profiles. We applied this strategy to mouse embryonic stem cells (mES), and adult brain, heart, kidney, and liver. Our results delineated 24,363 Pol II binding sites throughout the genome, 91% of which correspond to 5 end annotation based on known transcripts and cap-analysis of gene expression (CAGE) and can be regarded as promoters. A majority of these experimentally defined promoters are active in all tissues, while only 4,396 can be characterized as tissue-specific using a quantitative measure of Pol II occupancy. In general, Pol II occupancy at these tissue specific promoters is correlated with the presence of active histone modification marks. However, a set of mES- specific promoters display persistent levels of H3K4me3 in non-ES tissues despite undetectable Pol II binding and transcript. Broadly, our results expand the knowledge of tissue-specific mammalian genes and provide a resource for understanding the transcriptional programs in mammalian development and differentiation.
Publication Title
Genome-wide mapping and analysis of active promoters in mouse embryonic stem cells and adult organs.
Sample Metadata Fields
No sample metadata fields
View Samples