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SRP021513
Mus musculus
2 Downloadable Samples
Illumina Genome Analyzer II
Description
In this study, we employed massively parallel sequencing technology to identify miRNAs expressed in Zmpste24 WT MEF and Zmpste24-/- MEF. With data from 19.5 ×106 reads from WT MEFs and 16.5 × 106 reads from Zmpste24-/- MEFs, we discovered a total of 306 known miRNAs expressed in MEFs with a wide dynamic range of read counts ranging from 10 to over 1 million. A total of 8 miRNAs were found to be significantly down-regulated, with only 2 miRNAs upregulated, in Zmpste24-/- MEFs as compared to WT MEFs. Overall design: Examination of miRNA profile in Zmpste24 WT MEF and Zmpste24-/- MEF
Publication Title
MicroRNA transcriptome analysis identifies miR-365 as a novel negative regulator of cell proliferation in Zmpste24-deficient mouse embryonic fibroblasts.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dietary interventions are effective ways to extend or shorten lifespan. By examining midlife hepatic gene expressions in mice under different dietary conditions, which resulted in different lifespans and aging-related phenotypes, we were able to identify genes and pathways that modulate the aging process. We found that pathways transcriptionally correlated with diet-modulated lifespan and physiological changes were enriched for lifespan-modifying genes.
Publication Title
Midlife gene expressions identify modulators of aging through dietary interventions.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Dietary interventions are effective ways to extend or shorten lifespan. By examining midlife hepatic gene expressions in mice under different dietary conditions, which resulted in different lifespans and aging-related phenotypes, we were able to identify genes and pathways that modulate the aging process. To determine how our dietary intervention-based transcriptomic approach for predicting aging-regulatory genes compares to more traditional approach of using age-dependent transcriptional changes, we examined the hepatic gene expression changes in LF-fed mice during aging at 4, 8, 13 and 21 months.
Publication Title
Midlife gene expressions identify modulators of aging through dietary interventions.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 47 Downloadable Samples
- Illumina HiSeq 2000
Description
Epigenetic mechanisms including histone post-translational modifications control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging aspect of shortened lifespan, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a lifespan screen in S. cerevisiae, designed to identify altered amino acid residues of histones that alter yeast replicative aging. Our results reveal that lack of sustained H3K36 methylation is commensurate with increased cryptic transcription in a set of genes in old cells and shorter lifespan. Deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes and suppresses cryptic transcript initiation to extend lifespan. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to an increase in transcriptional noise that is detrimental to lifespan, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity. Overall design: This study examines transcription in yeast aging using a WT or Rph1 mutant background over a sequence of time-dependent FACS sorts of old cells. Cryptic transcripts are detected using a small fragment sequencing approach. The youngest WT yeast (designated S1Y, S2Y) are represented in seven biological replicates and one technical replicate, five small fragment and three others; the oldest WT yeast (designated S4O) are also represented in seven biological replicates and one technical replicate, again composed of five small fragment samples and three others. Intermediate WT yeast aging sorts (S2O and S3O) are each represented by five biological replicates and one technical replicate, three small fragment and three others. For mutant yeast, each stage in the time series is represented by five biological replicates and one technical replicate, three small fragment and three others. Experiment 4 is a technical replicate of experiment 3.
Publication Title
H3K36 methylation promotes longevity by enhancing transcriptional fidelity.
Sample Metadata Fields
Subject
View Samples- Caenorhabditis elegans
- 4 Downloadable Samples
- NextSeq 500
Description
Epigenetic mechanisms including histone post-translational modifications control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging aspect of shortened lifespan, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a lifespan screen in S. cerevisiae, designed to identify altered amino acid residues of histones that alter yeast replicative aging. Our results reveal that lack of sustained H3K36 methylation is commensurate with increased cryptic transcription in a set of genes in old cells and shorter lifespan. Deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes and suppresses cryptic transcript initiation to extend lifespan. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to an increase in transcriptional noise that is detrimental to lifespan, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity. Overall design: This study examines transcription in worm aging using FUDR treatment. The samples represent a time-series, with one control group without FUDR, and then three treated with FUDR at days 1, 8, and 12. Days 8 and 12 represent old worms. There are no replicates.
Publication Title
H3K36 methylation promotes longevity by enhancing transcriptional fidelity.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
We report that Dnmt1 is crucial during perinatal intestinal development. Loss of Dnmt1 in intervillus progenitor cells causes global hypomethylation, DNA damage, premature differentiation, and apoptosis, and consequently, loss of nascent villi. We further confirm the critical role for Dnmt1 during crypt development using the in vitro organoid culture system, and illustrate a clear differential requirement for Dnmt1 in immature versus mature organoids. These results demonstrate an essential role for Dnmt1 in maintaining genomic stability during intestinal development and the establishment of intestinal crypts. Overall design: We performed RNA-Seq of control and Dnmt1-ablated intestinal progenitor cells isolated from parrafin embedded tissues by laser capture microdissection (LCM).
Publication Title
Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Background and Aims: HNF4a is a nuclear hormone receptor transcription factor that has been shown to be required for hepatocyte differentiation and development of the liver. It has also been implicated in regulating expression of genes that act in the epithelium of the lower gastrointestinal tract. This implied that HNF4a might be required for development of the gut. Methods: We generated mouse embryos in which HNF4a was ablated in the epithelial cells of the fetal colon using Cre-loxP technology. Embryos were examined using a combination of histology, immunohistochemistry, gene array and RT-PCR, and chromatin immunoprecipitation analyses to define the consequence of loss of HNF4a on colon development. Results: Embryos could be generated until E18.5 that lacked HNF4a in their colon. Although, early stages of colonic development occurred, HNF4a null colons failed to form normal crypts. In addition, goblet cell maturation was perturbed and expression of an array of genes that encode proteins with diverse roles in colon function was disrupted. Several genes whose expression in the colon was dependent on HNF4a contained HNF4abinding sites sequences within putative transcriptional regulatory regions and a subset of these sites were occupied by HNF4a in vivo. Conclusion: HNF4a is a transcription factor that is essential for development of the mammalian colon, regulates goblet cell maturation and is required for expression of genes that control normal colon function and epithelial cell differentiation.
Publication Title
Hepatocyte nuclear factor 4alpha is essential for embryonic development of the mouse colon.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The composition of chromatin remodeling complexes dictates how these enzymes control transcriptional programs and cellular identity. Here, we investigate the composition of SWI/SNF complexes in embryonic stem cells (ESCs). In contrast to differentiated cells, ESCs have a biased incorporation of certain paralogous SWI/SNF subunits, with low levels of Brm, BAF170 and ARID1B. Upon differentiation, the expression of these subunits increases, resulting in a higher diversity of compositionally distinct SWI/SNF enzymes. We also identify Brd7 as a novel component of the PBAF complex in both ESCs and differentiated cells. Using shRNA-mediated depletion of Brg1, we show that SWI/SNF can function as both a repressor and an activator in pluripotent cells, regulating expression of developmental modifiers and signaling components such as Nodal, ADAMTS1, Bmi-1, CRABP1 and TRH. Knock-down studies of PBAF-specific Brd7 and of a signature subunit within the BAF complex, ARID1A, show that these two sub-complexes affect SWI/SNF target genes differentially, in some cases even antagonistically. This may be due to their different biochemical properties. Finally, we examine the role of SWI/SNF in regulating its target genes during differentiation. We find that SWI/SNF affects recruitment of components of the pre-initiation complex in a promoter-specific manner, to modulate transcription positively or negatively. Taken together, our results provide insight into the function of compositionally diverse SWI/SNF enzymes that underlie their inherent gene-specific mode of action.
Publication Title
BRD7, a novel PBAF-specific SWI/SNF subunit, is required for target gene activation and repression in embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 1 Downloadable Sample
Description
MicroRNAs fine-tune the activity of hundreds of protein-coding genes. The identification of tissue-specific microRNAs and their promoters has been constrained by the limited sensitivity of prior microRNA quantification methods. Here we determine the entire microRNAome of three endoderm-derived tissues, liver, small intestine, and pancreas, using ultra-high throughput sequencing. Although many microRNA genes are expressed at comparable levels, 162 microRNAs exhibited striking tissue-specificity. After mapping the promoters for these microRNA genes using H3K4me3 histone occupancy, we analyzed the regulatory modules of 63 microRNAs differentially expressed between liver and small intestine or pancreas. We determined that the same transcriptional regulatory mechanisms govern tissue-specific gene expression of both mRNA and microRNA encoding genes in mammals.
Publication Title
Tissue-specific regulation of mouse microRNA genes in endoderm-derived tissues.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we examined the effect of T cell-derived cytokines on retinal pigment epithelial (RPE) cells with respect to expression of complement components. We used an in vitro co-culture system in which CD3/CD28-activated human T cells were separated from the human RPE cell line (ARPE-19) by a membrane. Differential gene expression in the RPE cells of complement factor genes was identified using gene arrays, and selected gene transcripts were validated by q-RT-PCR. Protein expression was determined by ELISA and immunoblotting. Co-culture with activated T cells increased RPE mRNA and/or protein expression of complement components C3, factors B, H, H-like 1, CD46, CD55, CD59, and clusterin, in a dose-dependent manner. Soluble factors derived from activated T cells are capable of increasing expression of complement components in RPE cells. This is important for the further understanding of inflammatory ocular diseases such as uveitis and age-related macular degeneration.
Publication Title
Retinal pigment epithelial cells upregulate expression of complement factors after co-culture with activated T cells.
Sample Metadata Fields
Disease, Disease stage
View Samples