Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA269767 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-wide perturbations by miRNA map onto functional cancer pathways identifying regulators of chromatin modifiers
2015-03-31 | GSE64020 | GEO
Project description:Genome-wide perturbations by miRNA map onto functional cancer pathways identifying regulators of chromatin modifiers Total RNA obtained from cancer cell lines transfected with miR-365-3p for 24 hours compared to controls.
2015-03-31 | E-GEOD-64020 | biostudies-arrayexpress
Project description:Identifying processes occurring in early life affect subsequent life and health span is an urgent aim to improve human health. In this study, we identified a novel mechanism of dFOXO in longevity determination in Drosophila. We found that early adulthood induction of dFOXO is sufficient to reduce mortality in old age through different pathways than chronic dFOXO. We showed that dFOXO requires specific ATP-dependent chromatin modifiers to extend lifespan, and we could mimic this lifespan extension by modulating dFOXO’s targets in later life. Furthermore, dFOXO in early life induces a specific transcriptional programme that counteracts the natural transcriptomic changes occurring with age. Our findings provide a better understanding of transcriptional mechanisms related to longevity and opens new avenues for possible time-restricted interventions to improve human health in the future.
2022-09-28 | MTBLS3251 | MetaboLights
Project description:Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates, but the regulatory circuits specifying these states and enabling transitions between them are not well understood. We set out to address this issue and map the landscape of gene expression variability in PSCs by single-cell expression profiling of PSCs under different chemical and genetic perturbations. We find that signaling factors and developmental regulators show highly variable expression in PSCs, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signaling pathways and chromatin regulators. Strikingly, either removal of mature miRNAs or pharmacologic blockage of external signaling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency regulatory network, increased self-renewal efficiency, and a distinct chromatin state, an effect mediated by the action of opposing miRNA families on the c-myc / Lin28 / let-7 axis. These findings illuminate the causes of transcriptional heterogeneity in PSCs and their consequences for cellular decision-making.
2014-12-04 | GSE60749 | GEO
Project description:A number of transcriptional and chromatin regulatory proteins have been reported to be recruited to chromatin by specific regulatory RNAs. Whether RNA has a more general role in the interaction of proteins with chromatin is unknown. We used proteomics methods to determine the global impact of nascent RNA on chromatin in embryonic stem cells. Surprisingly, we found that nascent RNA primarily antagonises the interaction of chromatin modifiers and transcriptional regulators with chromatin. Transcriptional inhibition and RNA degradation induced recruitment of a set of transcriptional regulators, chromatin modifiers, nucleosome remodelers, and regulators of higher-order structure. RNA directly bound to factors including BAF, NuRD, EHMT1 and INO80 and inhibited their interaction with nucleosomes. In the case of the transcriptional elongation factor P-TEFb, direct binding to pre-mRNA released it from the chromatin-associated 7SK ribonucleoprotein complex. We propose that through these mechanisms, nascent RNA provides a direct link between transcriptional output and chromatin state.
2021-06-15 | PXD018706 | Pride
Project description:Pluripotent stem cells (PSCs) are capable of dynamic interconversion between distinct substates, but the regulatory circuits specifying these states and enabling transitions between them are not well understood. We set out to address this issue and map the landscape of gene expression variability in PSCs by single-cell expression profiling of PSCs under different chemical and genetic perturbations. We find that signaling factors and developmental regulators show highly variable expression in PSCs, with expression states for some variable genes heritable through multiple cell divisions. Expression variability and population heterogeneity can be influenced by perturbation of signaling pathways and chromatin regulators. Strikingly, either removal of mature miRNAs or pharmacologic blockage of external signaling pathways drives PSCs into a low-noise ground state characterized by a reconfigured pluripotency regulatory network, increased self-renewal efficiency, and a distinct chromatin state, an effect mediated by the action of opposing miRNA families on the c-myc / Lin28 / let-7 axis. These findings illuminate the causes of transcriptional heterogeneity in PSCs and their consequences for cellular decision-making. Single-cell RNA-Seq on 183 individual v6.5 mouse embryonic stem cells (mESCs) cultured in serum+LIF media, 94 v6.5 mESCs cultured in 2i+LIF media ('ground state' conditions), and 84 Dgcr8 -/- mESCs (constructed in a v6.5 background), that lack mature miRNAs due to knockout of a miRNA processing factor, cultured in serum+LIF. ChIP-Seq for RNA polymerase II, H3K4me3, H3K27me3, H3K27ac, H3K9me3, and H3K36me3 on the three populations of mESCs profiled by single-cell RNA-Seq. Single-cell RNA-Seq on 54 individual nestin-positive neural precursor cells derived from v6.5 mESCs.
2014-12-04 | E-GEOD-60749 | biostudies-arrayexpress
Project description:<p>Our current understanding of autism spectrum disorders (ASD) delineates a highly heritable, yet etiologically heterogeneous disease. Forward genetic approaches to find disease associated mutations or common variation have been successful and continue to offer considerable power. Yet, given the accumulating evidence for very significant heterogeneity and environmental influences, complementary approaches to classic forward genetics become necessary. Genetic polymorphism and mutation data to date have identified dozens of causal or contributory variants, yet our preliminary data from autism brain suggest that common molecular pathways are involved in a significant subset of cases. This convergence at the tissue level suggests that other mechanisms, specifically epigenetic changes, combined with genetic background, are contributing to such final common pathways. We further tested this hypothesis by taking a comprehensive and integrative genome-wide approach to assessing brain gene-expression, miRNA levels and the related, causal epigenetic mechanisms in ASD etiology. </p> <p>We performed RNA-seq analyses of four cerebral cortical regions and cerebellum from ASD cases and controls, to assess mRNA, miRNA, and splicing isoform regulation. In parallel, we identified key differences in chromatin state and DNA methylation across multiple brain regions in the same ASD and control individuals used in the expression analyses using ChIP-Seq and MeDIP. We assessed the mechanisms by which changes in DNA methylation, histone modification, and DNA sequence contribute to the observed differences in gene expression. This work, which represents an unprecedented effort to unify these often disparate data (usually produced without integration in mind), delineates potential shared molecular pathways in ASD and the underlying mechanism of these differences at the level of miRNA, the chromatin regulatory apparatus, and DNA methylation.</p> <p>The following substudies are part of the PsychENCODE release at dbGaP and offer additional molecular data: <ul> <li>PsychENCODE: RNA-Sequencing - SRRM4 Splicing Study <a href="study.cgi?study_id=phs000872">phs000872</a></li> <li>PsychENCODE: Global Changes in Patterning, Splicing and lncRNAs <a href="study.cgi?study_id=phs001061">phs001061</a></li> <li>PsychENCODE: Chromatin Contact Map in Fetal Cortical Laminae <a href="study.cgi?study_id=phs001190">phs001190</a></li> <li>PsychENCODE: Epigenetic Dysregulation in Autism Spectrum Disorder <a href="study.cgi?study_id=phs001220">phs001220</a></li> </ul> </p>
| phs001022 | dbGaP
Project description:The goal of the study was to determine whether perturbations in signaling pathways or chromatin regulators were sufficient to induce the illegitimate expression of tissue-restricted genes in primary human cells
2019-01-30 | GSE124111 | GEO
Project description:The goal of the study was to determine whether perturbations in signaling pathways or chromatin regulators were sufficient to induce the illegitimate expression of tissue-restricted genes in primary human cells
2019-01-30 | GSE124101 | GEO
Project description:Previously, we reported that Ambra1 is a core component of a cytoplasmic trafficking network, acting as a spatial rheostat to control active Src and FAK levels in addition to its critical roles in autophagy during neurogenesis. Here we identify a novel nuclear scaffolding function for Ambra1 that controls gene expression. Ambra1 binds to nuclear pore proteins, to other adaptor proteins like FAK and Akap8 in the nucleus, as well as to chromatin modifiers and transcriptional regulators such as Brg1, Cdk9 and the cAMP-regulated transcription factor Atf2. Ambra1 contributes to their association with chromatin and we identified genes whose transcription is regulated by Ambra1 complexes, likely via histone modifications and phospho-Atf2-dependent transcription. Therefore, Ambra1 scaffolds protein complexes at chromatin, regulating transcriptional signalling in the nucleus; in particular, it recruits chromatin modifiers and transcriptional regulators to control expression of genes such as Angpt1, Tgfb2, Tgfb3, Itga8 and Itgb7 that likely contribute to the role of Ambra1 in cancer cell invasion.
2021-09-09 | PXD018745 | Pride