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SRP162582
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well- characterized, but little is known about the mechanisms by which ADs effect gene activation. Here we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation. Overall design: RNA-seq in mouse embryonic stem cells after OCT4 degradation or LIF withdrawal
Publication Title
Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2500
Description
Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. We recently proposed that a phase-separated multi-molecular assembly underlies the formation and function of SEs. Here, we demonstrate that the SE-enriched factors BRD4 and MED1 form nuclear puncta that occur at SEs and exhibit properties of liquid-like condensates. Disruption of BRD4 and MED1 puncta by 1,6-hexanediol is accompanied by a loss of BRD4 and MED1 at SEs and a loss of RNAPII from SE-driven genes. We find that the intrinsically disordered regions (IDRs) of BRD4 and MED1 are sufficient to form phase-separated droplets in vitro and the MED1 IDR promotes phase separation in living cells. The MED1 IDR droplets are capable of compartmentalizing BRD4 and other transcriptional machinery in nuclear extracts. These results support the idea that SEs form phase-separated condensates that compartmentalize the transcription apparatus at key genes, provide insights into the role of cofactor IDRs in this process, and offer new insights into mechanisms involved in control of key cell identity genes. Overall design: polyA RNA-Seq in mouse embryonic stem cells
Publication Title
Coactivator condensation at super-enhancers links phase separation and gene control.
Sample Metadata Fields
Specimen part, Subject
View Samples- Oryza sativa, Arabidopsis thaliana
- 16 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
In this study, we used a cross-species network approach to uncover nitrogen (N)-regulated network modules conserved across a model and a crop species. By translating gene network knowledge from the data-rich model Arabidopsis (Arabidopsis thaliana, ecotype Columbia-0) to a crop, rice (Oryza sativa spp. japonica (Nipponbare)), we identified evolutionarily conserved N-regulatory modules as targets for translational studies to improve N use efficiency in transgenic plants.
Publication Title
Cross-Species Network Analysis Uncovers Conserved Nitrogen-Regulated Network Modules in Rice.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 424 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Background: Obesity is a risk factor for breast cancer in postmenopausal women and is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, molecular mechanisms through which excess adiposity influences breast cancer etiology are not well-defined.
Publication Title
Effect of obesity on molecular characteristics of invasive breast tumors: gene expression analysis in a large cohort of female patients.
Sample Metadata Fields
Disease stage
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Identifying PDEF regulated genes may shed light on the mechanism by which PDEF may induce breast cancer progression. To that purpose, we have used the MCF-7 human breast tumor cell line model to identify PDEF induced genes. Briefly, PDEF expression was down regulated by shRNA in MCF-7 cells and RNA probes from PDEF-down regulated and control MCF-7 cells were used to screen the Affymetrics HG-U133A Gene Chips. This analysis found 62 genes that were induced 2-fold or higher by PDEF. Further analysis of 3 of these genes namely S100A7, CEACAM6 and B7-H4 in primary breast tumors showed CEACAM6 as a frequently elevated and co-exressed gene with PDEF in these tumors.
Publication Title
Prostate derived Ets transcription factor and Carcinoembryonic antigen related cell adhesion molecule 6 constitute a highly active oncogenic axis in breast cancer.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Reprogramming resident glia into functional and subtype-specific neurons in vivo by delivering reprogramming genes directly to the brain provides a step forward towards the possibility of treating brain injuries or diseases. Here, we show that neurons reprogrammed using Ascl1, Lmx1a and Nurr1 functionally mature and integrate into existing brain circuitry, and that the majority of the reprogrammed neurons have properties of fast spiking, parvalbumin-containing interneurons. Overall design: A total of 6 samples were analyzed. Each sample is consists of approximately 33 laser-captured reprogrammed-neurons identified by nuclear GFP and expressing the transcription factors Ascl1, Lmx1a and Nurr1 (ALN).
Publication Title
Direct Reprogramming of Resident NG2 Glia into Neurons with Properties of Fast-Spiking Parvalbumin-Containing Interneurons.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 35 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
Rationale: Neonatal mice have the capacity to regenerate their hearts in response to injury, but this potential is lost after the first week of life. The transcriptional changes that underpin mammalian cardiac regeneration have not been fully characterized at the molecular level. Objective: The objectives of our study were to determine if myocytes revert the transcriptional phenotype to a less differentiated state during regeneration and to systematically interrogate the transcriptional data to identify and validate potential regulators of this process. Methods and Results: We derived a core transcriptional signature of injury-induced cardiac myocyte regeneration in mouse by comparing global transcriptional programs in a dynamic model of in vitro and in vivo cardiac myocyte differentiation, in vitro cardiac myocyte explant model, as well as a neonatal heart resection model. The regenerating mouse heart revealed a transcriptional reversion of cardiac myocyte differentiation processes including reactivation of latent developmental programs similar to those observed during de-stabilization of a mature cardiac myocyte phenotype in the explant model. We identified potential upstream regulators of the core network, including interleukin 13 (IL13), which induced cardiac myocyte cell cycle entry and STAT6/STAT3 signaling in vitro. We demonstrate that STAT3/periostin and STAT6 signaling are critical mediators of IL13 signaling in cardiac myocytes. These downstream signaling molecules are also modulated in the regenerating mouse heart. Conclusions: Our work reveals new insights into the transcriptional regulation of mammalian cardiac regeneration and provides the founding circuitry for identifying potential regulators for stimulating heart regeneration. Overall design: Comparison of transcriptional programs of primary myocardial tissues sampled from neonatal mice and murine hearts undergoing post-injury regeneration, along with in vitro ESC-differentiated cardiomyocytes
Publication Title
Transcriptional reversion of cardiac myocyte fate during mammalian cardiac regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Here, we examined the host response relative of SACC-PHHs infected with either hepatitis B virus (HBV) alone or both HBV/hepatitis delta virus (HDV) co-infection compared to non-infected controls. Overall design: SACC-PHHs were generated with PHHs from either a single human donor or mixed donors (in total, there were five donors) and co-cultured with 3T3J mouse non-parenchymal cells. These cultures can be persistently infected for up to 1-1.5 months post-challenge and exhibit a transcriptomic profile similar to what's observed in the 3D context of the liver. Note that not all donors and conditions have the same number of replicates.
Publication Title
Analysis of Host Responses to Hepatitis B and Delta Viral Infections in a Micro-scalable Hepatic Co-culture System.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Oryza sativa indica group
- 14 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Detailed analysis of genome-wide transcriptome profiling in rice root is reported here, following Cr-plant interaction. Such studies are important for the identification of genes responsible for tolerance, accumulation and defense response in plants with respect to Cr stress. Rice root metabolome analysis was also carried out to relate differential transcriptome data to biological processes affected by Cr (VI) stress in rice.
Publication Title
Transcriptomic and metabolomic shifts in rice roots in response to Cr (VI) stress.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We interrogated the transcriptome using RNA-seq at several stages of an mouse embryonic stem cell to cardiomyocyte directed differentiation protocol. These four stages represent timepoints when differentiating cultures are enriched for embryonic stem cells (ESC), mesodermal cells (MES), cardiac precursors (CP), or cardiomyocytes (CM) respectively. This study revealed many dynamic patterns of mRNAs and long non-coding RNAs (lncRNAs) and identified groups of genes with similar expression patterns during differentiation. Overall design: RNA-seq analysis of global RNA levels at 4 stages of directed cardiac differentiation of mouse embryonic stem cells. Each stage in biological duplicates
Publication Title
Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples