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GSE46209
Mus musculus
21 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The mammalian telomere-binding protein Rap1 was found to have additional non-telomeric functions, acting as a transcriptional cofactor and a regulator of the NF-kB pathway. Here, we assess the effect of disrupting mouse Rap1 in vivo, and report on its unanticipated role in metabolic regulation and body weight homeostasis. Rap1 inhibition causes dysregulation in hepatic as well as adipose function. In addition, using a separation-of-function allele, we show that the metabolic function of Rap1 is independent of its recruitment to TTAGGG binding elements found at telomeres, and at other interstitial loci.
Publication Title
Nontelomeric role for Rap1 in regulating metabolism and protecting against obesity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BMP9 signaling has been implicated in hereditary hemorrhagic telangiectasia and vascular remodeling, acting via the HHT target genes, endoglin and ALK1. This study sought to identify endothelial BMP9-regulated proteins that could affect the HHT phenotype. Gene ontology analysis of cDNA microarray data obtained following BMP9 treatment of primary human endothelial cells indicated regulation of chemokine, adhesion, and inflammation pathways.
Publication Title
BMP9 regulates endoglin-dependent chemokine responses in endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
IonTorrentProton
Description
Purpose: mRNA translation into protein is highly regulated, but the role of mRNA isoforms, noncoding RNAs (ncRNAs), and genetic variants has yet to be systematically studied. Using high-throughput sequencing (RNA-seq), we have measured cellular levels of mRNAs and ncRNAs, and their isoforms, in lymphoblast cell lines (LCL) and in polysomal fractions, the latter shown to yield strong correlations of mRNAs with expressed protein levels. Analysis of allelic RNA ratios at heterozygous SNPs served to reveal genetic factors in ribosomal loading. Methods: RNA-seq was performed on cytosolic extracts and polysomal fractions (3 ribosomes or more) from three lymphoblastoid cell lines. As each RNA fraction was amplified (NuGen kit), and relative contributions from various RNA classes differed between cytosol and polysomes, the fraction of any given RNA species loaded onto polysomes was difficult to quantitate. Therefore, we focused on relative recovery of the various RNA classes and rank order of single RNAs compared to total RNA. Results: RNA-seq of coding and non-coding RNAs (including microRNAs) in three LCLs revealed significant differences in polysomal loading of individual RNAs and isoforms, and between RNA classes. Moreover, correlated distribution between protein-coding and non-coding RNAs suggests possible interactions between them. Allele-selective RNA recruitment revealed strong genetic influence on polysomal loading for multiple RNAs. Allelic effects can be attributed to generation of different RNA isoforms before polysomal loading or to differential loading onto polysomes, the latter defining a direct genetic effect on translation. Several variants and genes identified by this approach are also associated with RNA expression and clinical phenotypes in various databases. Conclusions: These results provide a novel approach using complete transcriptome RNA-seq to study polysomal RNA recruitment and regulatory variants affecting protein translation. Overall design: cells from 3 samples were grown to 5x105 cells/mL density in T75 tissue culture flask and harvested, total RNA and polysome bound RNA was sequenced by Ion Proton
Publication Title
Allele-Selective Transcriptome Recruitment to Polysomes Primed for Translation: Protein-Coding and Noncoding RNAs, and RNA Isoforms.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Identifying target genes of the two human chromatin remodeling enzymes CHD3 and CHD4 Methods: see below in protocols Results: Libraries were sequenced on Illumina HiSeq2000 platform resulting in 37-71 Mio 50 bp paired-end reads per sample. We identified 16 (i) and 115 (ii) distinctly regulated genes when CHD3-GFP (i) or CHD4-GFP (ii) were overexpressed. Nine genes seem to be commonly regulated by CHD3 and CHD4. We successfully validated four genes from our RNA-seq via qPCR with two new (independent from those, used for RNA-seq) biological replicates. Conclusion: CHD3 and CHD4 regulate distinct genes. Overall design: Total RNA was prepared from 24 hours induced (1 ng/µl Dox) and non-induced Flp-In™ T-REx™ 293 cells, expressing GFP, hCHD3-GFP (UniProt: Q12873) or hCHD4-GFP(UniProt Q14839). Library preparation and Illumina Sequencing was perfprmed by EMBL GeneCore facility in Heidelberg (Germany: Dr. Vladimir Benes)
Publication Title
CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
KAP1 regulates gene networks controlling T-cell development and responsiveness.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The modulation of chromatin status at specific genomic loci controls lymphoid differentiation. Here, we investigated the role played in this process by KAP1, the universal cofactor of KRAB-containing Zinc Finger Proteins (KRAB-ZFPs), a tetrapod-restricted family of transcriptional repressors. T cell-specific Kap1 knockout mice displayed a significant expansion of immature thymocytes and imbalances in the ratios of mature T cells in the thymus and the spleen, with impaired responses to TCR stimulation. Transcriptome and chromatin studies revealed that KAP1 directly controls the expression of a number of genes involved in TCR and cytokine signalling, among which Traf1 and FoxO1, and is strongly associated with cis-acting regulatory elements marked by the H3K9me3 repressive mark on the genome of thymic T cells. Likely responsible for tethering KAP1 to at least part of its genomic targets, a small number of KRAB/ZFPs are selectively expressed in T lymphoid cells. These results reveal the so far unsuspected yet important role of KRAB/KAP1-mediated epigenetic regulation in T lymphocyte differentiation and activation.
Publication Title
KAP1 regulates gene networks controlling T-cell development and responsiveness.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Global heterochromatin reduction, which is one of the hallmarks of aging cells, is associated with reduced transposable element repression and increased risk of chromatin instability. To ensure genomic integrity, the irreparable cells in a population exit permanently from the cell cycle, and this process is termed “senescence”. However, senescence only blocks the expansion of unwanted cells, and the aberrant chromatin of senescent cells remains unstable. Serendipitously, we found that the transient ectopic expression of a repressive epigenetic modulator, DNA methyltransferase 3-like (DNMT3L) was sufficient to delay the premature senescence progression of late-passage mouse embryonic fibroblasts (MEFs) associated with a tightened global chromatin structure. DNMT3L induces more repressive H3K9 methylation on endogenous retroviruses and downregulates the derepressed transposons in aging MEFs. In addition, we found that a pulse of ectopic DNMT3L resulted in the reestablishment of H3K27me3 on polycomb repressive complex 2 (PRC2)-target genes that were derepressed in old MEFs. We demonstrated that ectopic DNMT3L interacted with PRC2 in MEFs. Our data also suggested that ectopic DNMT3L might guide PRC2 to redress deregulated chromatin regions in aging cells. This study might lead to an epigenetic reinforcement strategy for overcoming aging-associated epimutation and senescence.
Publication Title
Transient DNMT3L Expression Reinforces Chromatin Surveillance to Halt Senescence Progression in Mouse Embryonic Fibroblast.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Chromatin remodeling is fundamental for B cell differentiation. Here, we explored the role in this process of KAP1, the cofactor of KRAB-ZFP transcriptional repressors. B lymphoid-specific Kap1 knockout mice displayed reduced numbers of mature B cells, lower steady-state levels of antibodies and accelerated rates of decay of neutralizing antibodies following viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an upregulation of PTEN, the enzymatic counter-actor of PIK3 signaling, and of genes encoding DNA damage response factors, cell-cycle regulators and chemokine receptors. ChIP/seq studies established that KAP1 bound at or close to a number of these genes, and controlled chromatin status at their promoters. Genome-wide, KAP1-binding sites avoided active B cell-specific enhancers and were enriched in repressive histone marks, further supporting a role for this molecule in gene silencing in vivo. Likely responsible for tethering KAP1 to at least some of these targets, a discrete subset of KRAB-ZFPs is enriched in B lymphocytes. This work thus reveals the role of KRAB/KAP1-mediated epigenetic regulation in B cell development and homeostasis.
Publication Title
KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
E-cadherin, a protein encoded by the CDH1 gene is the dominant epithelial cell adhesion molecule playing a crucial role in epithelial tissue polarity and structural integrity. The progression of 90% or more carcinomas is believed to be mediated by disruption of normal E-cadherin expression, subcellular localization or function. Despite the strong correlation between E-cadherin loss and malignancy the mechanism through how this occurs is not known in most sporadic and hereditary epithelial carcinomas. Previous works have shown the importance of CDH1 intron 2 sequences for proper gene and protein expression supporting the possibility of these being cis-modulators of E-cadherin expression/function. but when co-expressed it led to reduced cell-cell adhesiveness, increased invasion and angiogenesis. By expression array analysis, IFITM1 and IFI27 levels were found to be increased upon CDH1a overexpression. Importantly, CDH1a was found to be de novo expressed in gastric cancer cell lines when compared to normal stomach.
Publication Title
Transcription initiation arising from E-cadherin/CDH1 intron2: a novel protein isoform that increases gastric cancer cell invasion and angiogenesis.
Sample Metadata Fields
Specimen part, Cell line
View Samples