Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA137677 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR097854.fastq.gz | Fastqsanger.gz | |||
| SRR097855.fastq.gz | Fastqsanger.gz | |||
| SRR097856.fastq.gz | Fastqsanger.gz | |||
| SRR097857.fastq.gz | Fastqsanger.gz | |||
| SRR097858.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 11 |
Similar Datasets
Project description:Transcription Pausing Regulates Mouse Embryonic Stem Cell Differentiation [ATAC-seq]
| PRJNA389551 | ENA
Project description:Transcription Pausing Regulates Mouse Embryonic Stem Cell Differentiation [GRO-seq]
| PRJNA389560 | ENA
Project description:TRIM28 regulates RNA polymerase II promoter proximal pausing and entry into processive elongation
| PRJNA209380 | ENA
Project description:Signal-dependent RNA Polymerase II (Pol2) productive elongation is an integral component of gene transcription, including those of immediate early genes (IEGs) induced by neuronal activity. However, it remains unclear how productively elongating Pol2 overcome nucleosomal barriers. Using RNAi, three degraders, and several small molecule inhibitors, we show that the mammalian SWI/SNF complex of neurons (neuronal BAF, or nBAF) is required for activity-induced transcription of neuronal IEGs, including Arc. The nBAF complex facilitates promoter-proximal Pol2 pausing, signal-dependent Pol2 recruitment (loading), and importantly, mediates productive elongation in the gene body via interaction with the elongation complex and elongation-competent Pol2. Mechanistically, Pol2 elongation is mediated by activity-induced nBAF assembly (especially, ARID1A recruitment) and its ATPase activity. Together, our data demonstrate that the nBAF complex regulates several aspects of Pol2 transcription and reveal mechanisms underlying activity-induced Pol2 elongation. These findings may offer insights into human maladies etiologically associated with mutational interdiction of BAF functions.
2024-06-18 | PXD052840 | JPOST Repository
Project description:In vitro studies identified various factors including P-TEFb, SEC, SPT6, PAF1, DSIF, and NELF functioning at different stages of transcription elongation driven by RNA polymerase II (RNA Pol II). What remains unclear is how these factors cooperatively regulate pause/release and productive elongation in the context of living cells. Using an acute 5 protein-depletion approach, prominent release and a subsequent increase in mature transcripts, whereas long genes fail to yield mature transcripts due to a loss of processivity. Mechanistically, loss of SPT6 results in loss of PAF1 complex (PAF1C) from RNA Pol II, leading to NELF-bound RNA Pol II release into the gene bodies. Furthermore, SPT6 and/or PAF1 depletion impairs heat shock-induced pausing, pointing to a role for SPT6 in regulating RNA Pol II pause/release through the recruitment of PAF1C during the early elongation.
2022-08-09 | PXD033771 | Pride
Project description:Trimethylation of histone H3 lysine 4 (H3K4me3) is associated with transcriptional start sites and proposed to regulate transcription initiation. However, redundant functions of the H3K4 SET1/COMPASS methyltransferase complexes complicate elucidation of the specific role of H3K4me3 in transcriptional regulation. Here, by using mouse embryonic stem cells (mESCs) as a model system, we show that acute ablation of shared subunits of the SET1/COMPASS complexes leads to complete loss of all H3K4 methylation. H3K4me3 turnover occurs more rapidly than H3K4me1 and H3K4me2 and is dependent on KDM5 demethylases. Surprisingly, acute loss of H3K4me3 does not have detectable effects on transcriptional initiation but leads to a widespread decrease in transcriptional output, an increase in RNA polymerase II (RNAPII) pausing and slower elongation. Notably, we show that H3K4me3 is required for the recruitment of the Integrator Complex Subunit 11 (INTS11), which is essential for the eviction of paused RNAPII and transcriptional elongation. Thus, our study demonstrates a distinct role for H3K4me3 in transcriptional pause-release and elongation rather than transcriptional initiation.
2023-02-10 | PXD039176 | Pride
Project description:RNA polymerase II promoter-proximal pausing is orchestrated by a ribonucleoprotein complex scaffolded by the noncoding RNA Rn7sk. However, how this interruption of transcription is mechanistically linked to RNA production remains largely unknown. Here, we show that forcing the pause release by germ-line deletion of Rn7sk was embryonic lethal, yet conditional deletion of Rn7sk enhanced stem cell differentiation in skin. To explore the immediate transcriptional mechanisms underpinning enhanced differentiation, we metabolically labelled newly-synthesized RNAs after Rn7sk deletion. Unexpectedly, forced pause release robustly repressed transcription specifically at cell cycle regulators, in the absence of chromatin remodeling at promoters and enhancers. Our results indicate that polymerase pausing affords the core elongation machinery time to properly assemble, and forced elongation triggers splicing defects and nuclear RNA decay. Cell cycle regulators appear highly sensitive to mis-regulation of the elongation machinery due to unique genomic features of high promoter accessibility and low GC–content in the gene body. Transcriptional pausing thus serves as a rate-limiting step in controlling cell division.
2021-08-12 | GSE101216 | GEO
Project description:RNA polymerase II promoter-proximal pausing is orchestrated by a ribonucleoprotein complex scaffolded by the noncoding RNA Rn7sk. However, how this interruption of transcription is mechanistically linked to RNA production remains largely unknown. Here, we show that forcing the pause release by germ-line deletion of Rn7sk was embryonic lethal, yet conditional deletion of Rn7sk enhanced stem cell differentiation in skin. To explore the immediate transcriptional mechanisms underpinning enhanced differentiation, we metabolically labelled newly-synthesized RNAs after Rn7sk deletion. Unexpectedly, forced pause release robustly repressed transcription specifically at cell cycle regulators, in the absence of chromatin remodeling at promoters and enhancers. Our results indicate that polymerase pausing affords the core elongation machinery time to properly assemble, and forced elongation triggers splicing defects and nuclear RNA decay. Cell cycle regulators appear highly sensitive to mis-regulation of the elongation machinery due to unique genomic features of high promoter accessibility and low GC–content in the gene body. Transcriptional pausing thus serves as a rate-limiting step in controlling cell division.
2021-08-12 | GSE101215 | GEO
Project description:Gene expression is regulated by controlling distinct steps of the transcriptional cycle, including initiation, pausing, elongation, and termination. Kinases phosphorylate RNA Polymerase II and associated factors to control transitions between these steps and act as central gene regulatory nodes. Similarly, phosphatases that dephosphorylate these components are emerging as important regulators of transcription, though their roles remain less well understood. Here we discover that the PNUTS-PP1 phosphatase complex plays an essential role in controlling transcription pause release in addition to its previously described function in transcription termination. Transcription pause release by the PNUTS complex is essential for almost all RNA Pol II-dependent gene transcription, relies on its PP1 phosphatase subunit, and controls the phosphorylation of factors required for pause release and elongation. Together, this reveals an essential new role for a phosphatase complex in transcription pause release and shows that the PNUTS complex is essential for RNA Poll II-dependent transcription.
2024-06-28 | MSV000095177 | MassIVE
Project description:Chickarmane2006 - Stem cell switch reversible
Kinetic modeling approach of the transcriptional dynamics of the embryonic stem cell switch.
This model is described in the article:
Transcriptional dynamics of the embryonic stem cell switch.
Chickarmane V, Troein C, Nuber UA, Sauro HM, Peterson C
PLoS Computational Biology. 2006; 2(9):e123
Abstract:
Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG. In addition to regulating each other through feedback loops, these genes also regulate downstream target genes involved in the maintenance and differentiation of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other species reveals that it is unique to mammals. With a kinetic modeling approach, we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible assumptions about the interactions between the transcription factors at the gene promoter binding sites and RNA polymerase (RNAP), at each of the three genes as well as at the target genes. We identify a bistable switch in the network, which arises due to several positive feedback loops, and is switched on/off by input environmental signals. The switch stabilizes the expression levels of the three genes, and through their regulatory roles on the downstream target genes, leads to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is on, the self-renewal genes are on and the differentiation genes are off. The opposite holds when the switch is off. The model is extremely robust to parameter changes. In addition to providing a self-consistent picture of the transcriptional circuit, the model generates several predictions. Increasing the binding strength of NANOG to OCT4 and SOX2, or increasing its basal transcriptional rate, leads to an irreversible bistable switch: the switch remains on even when the activating signal is removed. Hence, the stem cell can be manipulated to be self-renewing without the requirement of input signals. We also suggest tests that could discriminate between a variety of feedforward regulation architectures of the target genes by OCT4, SOX2, and NANOG.
This model is hosted on BioModels Database
and identified by: MODEL7957907314
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000203 | BioModels