Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA321970 | ENA |
REPOSITORIES: ENA
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Project description:Dynamic regulation of gene expression via signal transduction pathways is of fundamental importance during many biological processes such as cell state transitioning, cell cycle progression and stress responses. In this study we used serum stimulation as a cell response paradigm to apply the nascent RNA Bru-seq technique in order to capture early dynamic changes in the nascent transcriptome. Our data provides an unprecedented view of the dynamics of genome- wide transcription during the first two hours of serum stimulation in human fibroblasts. While some genes showed sustained induction or repression, other genes showed transient or delayed responses. Surprisingly, the dynamic patterns of induction and suppression of response genes showed a high degree of similarity, suggesting that these opposite outcomes are triggered by a common set of signals. As expected, early response genes such as those encoding components of the AP-1 transcription factor and those involved in the circadian clock were immediately but transiently induced. Surprisingly, transcription of important DNA damage response genes and histone genes were rapidly repressed.We also show that RNA polymerase II accelerates as it transcribes large genes and this was independent of whether the gene was induced or not. These results provide a unique genome-wide depiction of dynamic patterns of transcription of serum response genes and demonstrate the utility of Bru-seq to comprehensively capture rapid and dynamic changes of the nascent transcriptome.
2016-05-20 | GSE81548 | GEO
Project description:Regulation of the translatome is essential during stress. However, the precise sets of translational targets regulated by the key translational stress responses –integrated stress response (ISR) and mTORC1 – remain elusive. We developed multiplexed enhanced protein dynamics (mePROD) proteomics, combining dynamic SILAC, multiplexing, and signal amplification, to enable measuring acute changes in protein synthesis. Treating cells with ISR/mTORC1-modulating stressors, we showed extensive translatome modulation and ~20% of proteins synthesized at highly reduced rates. Comparing translation-deficient sub-proteomes revealed an extensive overlap demonstrating that target specificity is achieved on protein level and not by pathway activation. Titrating inhibition of cap-dependent translation confirmed that synthesis of individual proteins is controlled by intrinsic properties responsive to global translation inhibition. This study reports a method to measure translation rates at the nascent chain level and provides insight into how the ISR and mTORC1, two key cellular pathways, regulate the translatome to guide cellular survival upon stress.
2019-12-09 | PXD015438 | Pride
Project description:Regulation of the translatome is essential during stress. However, the precise sets of translational targets regulated by the key translational stress responses –integrated stress response (ISR) and mTORC1 – remain elusive. We developed multiplexed enhanced protein dynamics (mePROD) proteomics, combining dynamic SILAC, multiplexing, and signal amplification, to enable measuring acute changes in protein synthesis. Treating cells with ISR/mTORC1-modulating stressors, we showed extensive translatome modulation and ~20% of proteins synthesized at highly reduced rates. Comparing translation-deficient sub-proteomes revealed an extensive overlap demonstrating that target specificity is achieved on protein level and not by pathway activation. Titrating inhibition of cap-dependent translation confirmed that synthesis of individual proteins is controlled by intrinsic properties responsive to global translation inhibition. This study reports a method to measure translation rates at the nascent chain level and provides insight into how the ISR and mTORC1, two key cellular pathways, regulate the translatome to guide cellular survival upon stress.
2019-12-06 | PXD014377 | Pride
Project description:Profiling the nascent cellular proteome and capturing early proteomic changes in response to external stimuli provides valuable insight into cellular physiology. Existing metabolic protein labelling approaches based on bioorthogonal methionine- or puromycin analogueues allow for the selective visualization and enrichment of the newly synthesized proteins, however, their applications are limited as they require methionine-free conditions or are toxic to cells. Here, we introduce a novel threonine-derived non-canonical amino acid tagging method, THRONCAT, based on bioorthogonal threonine analogueue β-ethynyl serine (βES) that enables efficient and non-toxic labelling of the nascent proteome in complete growth media within minutes. We used THRONCAT for the visualization and enrichment of nascent proteins in bacteria, mammalian cells, and drosophila melanogaster and rapidly profiled proteomic changes of Ramos B-cells in response to receptor activation in a time-stamp approach, demonstrating the potential and ease-of-use of the method.
2023-07-20 | PXD032368 | Pride
Project description:Genomic responses in blood during acute human anaphylaxis
| PRJNA207345 | ENA
Project description:Capturing drug responses by quantitative promoter activity profiling
| PRJNA210934 | ENA
Project description:Capturing drug responses by quantitative promoter activity profiling
| PRJDB1895 | ENA
Project description:Determination of dynamic changes in chromatin accessibility during cellular reprogramming [scRNA]
| PRJNA391419 | ENA
Project description:Determination of dynamic changes in chromatin accessibilty during cellular reprogramming [scATAC]
| PRJNA338877 | ENA
Project description:Exposure to heat stress triggers a well-defined acute response marked by HSF1-dependent transcriptional upregulation of heat shock proteins. Cells allowed to recover acquire thermotolerance, but this adaptation is poorly understood. By quantitative proteomics, we discovered selective upregulation of HSP70-family chaperone HSPA1 and its co-factors, HSPH1 and DNAJB1, in MCF7 breast cancer cells acquiring thermotolerance. HSPA1 was found to have dual function during heat stress response: (i) during acute stress, it promotes the recruitment of the 26S proteasome to translating ribosomes, thus poising cells for rapid protein degradation and resumption of protein synthesis upon recovery; (ii) during thermotolerance, HSPA1 together with HSPH1 maintains ubiquitylated nascent/newly synthesized proteins in a soluble state required for their efficient proteasomal clearance. Consistently, deletion of HSPH1 impedes thermotolerance and esophageal tumor growth in mice, thus providing a potential explanation for the poor prognosis of digestive tract cancers with low HSPH1, and nominating HSPH1 as a cancer drug target. We propose dual roles of HSPA1 either alone or in complex with HSPH1 and DNAJB1 in promoting quality control of nascent/newly synthesized proteins and cellular thermotolerance.
2021-05-02 | PXD025123 | Pride