Filters
Technology
Platform
SRP119967
Homo sapiens
16 Downloadable Samples
Illumina HiSeq 4000
Description
Transcription termination and mRNA export from the nucleus are closely regulated and coordinated processes. Nuclear export factors are recruited to actively transcribed genes through their interactions with protein complexes associated with transcription and co-transcriptional pre-mRNA processing. We determine a new role for the kinase WNK1 in the cross-talk of transcription termination and mRNA export. WNK1 was previously attributed a cytoplasmic role as a regulator of ion transport. However, we now show a nuclear function for this kinase where it is required for efficient mRNA export along with the transcription termination factor PCF11. Finally, we identify the phosphorylation of the CID domain of PCF11 as an important step for the release of the mRNA from the transcription locus, thus allowing efficient mRNA export to the cytoplasm. Overall design: RNA from cytoplasmic and nuclear extracts of HeLa cells was obtained, upon depletion of WNK1 kinase or from control cells. Upon pA selection, libraries were generated and sequenced. A duplicate experiment was performed for each sample.
Publication Title
WNK1 kinase and the termination factor PCF11 connect nuclear mRNA export with transcription.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 192 Downloadable Samples
- NextSeq 500
Description
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response. By evaluating human peripheral blood and NSCLC tumors, we show that the selective HDAC6 inhibitor ricolinostat promotes phenotypic changes that support enhanced T cell activation and improved function of antigen presenting cells. The bromodomain inhibitor JQ1 attenuated CD4+Foxp3+ T regulatory cell suppressive function and synergized with ricolinostat to facilitate immune-mediated tumor growth arrest, leading to prolonged survival of mice with lung adenocarcinomas. Collectively, our findings highlight the immunomodulatory effects of two epigenetic modifiers that, together, promote T cell-mediated anti-tumor immunity and demonstrate their therapeutic potential for treatment of NSCLC. Overall design: Single-cell comparison of vehicle (control) and HDAC inhibitor (ricolinostat)-treated tumor infiltrating T cells and macrophages
Publication Title
Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non-Small Cell Lung Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 96 Downloadable Samples
- NextSeq 500
Description
The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: Semi-nascent transcriptome measured by chromatin-bound RNA-seq in HeLa cells. Control and PCF11 knock-down (2 biological replicates) and control and PCF11 PAS1 deletion (4 biological replicates).
Publication Title
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 56 Downloadable Samples
- Illumina HiSeq 2500
Description
The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: 3' mRNA-seq in individual zebrafish embryo heads. Two types of mutants: zPCF11 null and zPCF11 with deletion of PAS1. Wild-type (wt, +/+), heterozygous (het, +/-) and homozygous mutant (hom, -/-) embryos were analyzed. Wild-type and heterozygous animals were phenotypically indistinguishable.
Publication Title
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3' mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination. Overall design: 3' mRNA-seq in HeLa cells. Control and PCF11 knock-down (4 biological replicates); control and PCF11 PAS1 deletion clones muA and muB (3 biological replicates); control and additional PCF11 PAS1 deletion clones muC and muD (1 replicate).
Publication Title
Selective Roles of Vertebrate PCF11 in Premature and Full-Length Transcript Termination.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
The effects of a histone demethylase inhibitor, GSK-J4, and L-ascorbic acid for the transcriptome in female ES cells were analyzed by RNA-sequence. Total RNA was used for high-throughput sequence with Illumina HiSeq 2500 and mapped to mm10. Overall design: Total RNA profile
Publication Title
Histone demethylation maintains Prdm14 and Tsix expression and represses xIst in embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
IL-2 signals into CD8 T cells have a programming and regulatory role in driving cells to full effector and memory differentiation. This study was designed to look for IL-2 target genes that affect CD8 T cell responses.
Publication Title
Endoplasmic reticulum stress regulator XBP-1 contributes to effector CD8+ T cell differentiation during acute infection.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 23 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Zebrafish (Danio rerio) gutGFP transgenic embryos [Tg(XlEef1a1:GFP)s854] were collected at 4 time points: 2 days post fertilization (dpf), 3, dpf, 4 dpf, 6 dpf. Embryos were dissociated into single cells and sorted by FACS based on GFP expression.
Publication Title
FACS-assisted microarray profiling implicates novel genes and pathways in zebrafish gastrointestinal tract development.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Purpose: To identify the changes in postnatal mouse conjunctival forniceal gene expression and their regulation by Klf4 around eye opening stage when the goblet cells first appear.
Publication Title
Mouse conjunctival forniceal gene expression during postnatal development and its regulation by Kruppel-like factor 4.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Chronic opiate use produces molecular and cellular adaptations in the nervous system, leading to tolerance, physical dependence and addiction. Genome-wide comparison of morphine-induced changes in brain transcription of mouse strains with different opioid-related phenotypes provides an opportunity to discover the relationship between gene expression and behavioral response to the drug.
Publication Title
Morphine effects on striatal transcriptome in mice.
Sample Metadata Fields
No sample metadata fields
View Samples