MYC Amplifies Gene Expression through Global Changes in Transcription Factor Dynamics
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA785239 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17085860_1.fastq.gz | Fastqsanger.gz | |||
| SRR17085860_2.fastq.gz | Fastqsanger.gz | |||
| SRR17085861_1.fastq.gz | Fastqsanger.gz | |||
| SRR17085861_2.fastq.gz | Fastqsanger.gz | |||
| SRR17085862_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:The MYC oncogene has been studied for decades, yet there is still intense debate over how this transcription factor controls gene expression. Here, we seek to answer these questions with an in vivo readout of discrete events of gene expression in single cells. We engineered an optogenetic variant of MYC (Pi-MYC) and combined this tool with single-molecule RNA and protein imaging techniques to investigate the role of MYC in modulating transcriptional bursting and transcription factor binding dynamics in human cells. We find that the immediate consequence of MYC overexpression is to increase the duration rather than frequency of bursts, a functional role which is different from the majority of human transcription factors. We further propose that the mechanism by which MYC exerts global effects on the active period of genes is by altering the binding dynamics of transcription factors involved in RNA Polymerase II complex assembly and productive elongation.
2021-12-07 | GSE189943 | GEO
Project description:The MYC oncogene has been studied for decades, yet there is still intense debate over how this transcription factor controls gene expression. Here, we seek to answer these questions with an in vivo readout of discrete events of gene expression in single cells. We engineered an optogenetic variant of MYC (Pi-MYC) and combined this tool with single-molecule RNA and protein imaging techniques to investigate the role of MYC in modulating transcriptional bursting and transcription factor binding dynamics in human cells. We find that the immediate consequence of MYC overexpression is an increase in the duration rather than in the frequency of bursts, a functional role that is different from the majority of human transcription factors. We further propose that the mechanism by which MYC exerts global effects on the active period of genes is by altering the binding dynamics of transcription factors involved in RNA polymerase II complex assembly and productive elongation.
| S-EPMC8849550 | biostudies-literature
Project description:Global expression profiling of Emu-myc lymphomas
| PRJNA167838 | ENA
Project description:We investigated global, actively transcribed, stable, and myonucleus-specific transcriptomes following an acute hypertrophic stimulus in mouse plantaris. With these datasets we define global and Myc-specific dynamics at the onset of rapid loading-induced muscle fiber growth.
2023-05-01 | GSE213406 | GEO
Project description:Global dynamics of stage-specific transcription factor binding during thymocyte development
| PRJNA418973 | ENA
Project description:Cell-to-cell heterogeneity is vital for tumor evolution and survival. How cancer cells achieve and exploit this heterogeneity remains an active area of research. Here we identify c-Myc as a highly heterogeneously expressed transcription factor, and an orchestrator of transcriptional and phenotypic diversity in cancer cells. By monitoring endogenous c-Myc protein in individual living cells, we uncovered the surprising pulsatile nature of c-Myc expression and the extensive cell-to-cell variability in its dynamics. We further demonstrated that heterogeneity in c-Myc dynamics leads to variable target gene transcription, and that timing of c-Myc expression predicts cell-cycle progression rates and drug sensitivities. Together, our data advocates for a model in which cancer cells increase the heterogeneity of functionally diverse transcription factors such as c-Myc to rapidly survey transcriptional landscapes and survive stress.
| EGAS00001007091 | EGA
Project description:Over-expression of the Myc transcription factor causes its widespread interaction with regulatory domains in the genome, but leads to the up- and down-regulation of discrete sets of genes. The molecular determinants of these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis of transcription and mRNA dynamics following Myc activation in proliferating mouse fibroblasts, based on chromatin immunoprecipitation, metabolic labeling of newly synthesized RNA, extensive sequencing and mathematical modeling. Transcriptional activation correlated with the highest increases in Myc binding at promoters. Repression followed a reciprocal scenario, with the lowest gains in Myc binding. Altogether, the relative abundance (henceforth, “share”) of Myc at promoters was the strongest predictor of transcriptional responses in diverse cell types, predominating over Myc’s association with the co-repressor Miz1. Myc activation elicited immediate loading of RNAPII at activated promoters, followed by increases in pause-release5, while repressed promoters showed opposite effects. Gains and losses in RNAPII loading were proportional to the changes in the Myc share, suggesting that repression by Myc may be largely indirect, owing - at least in part - to competition for limiting amounts of RNAPII. Secondary to the changes in RNAPII loading, the dynamics of elongation and pre-mRNA processing were also rapidly altered at Myc regulated genes, leading to the transient accumulation of partially or aberrantly processed mRNAs. Altogether, our results shed light on how over-expressed Myc alters the various phases of the RNAPII cycle and the resulting transcriptional response.
2017-08-23 | GSE98420 | GEO
Project description:Global analyses of the dynamics of miRNA metabolism
| PRJNA531270 | ENA
Project description:Over-expression of the Myc transcription factor causes its widespread interaction with regulatory domains in the genome, but leads to the up- and down-regulation of discrete sets of genes. The molecular determinants of these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis of transcription and mRNA dynamics following Myc activation in proliferating mouse fibroblasts, based on chromatin immunoprecipitation, metabolic labeling of newly synthesized RNA, extensive sequencing and mathematical modeling. Transcriptional activation correlated with the highest increases in Myc binding at promoters. Repression followed a reciprocal scenario, with the lowest gains in Myc binding. Altogether, the relative abundance (henceforth, “share”) of Myc at promoters was the strongest predictor of transcriptional responses in diverse cell types, predominating over Myc’s association with the co-repressor Miz1. Myc activation elicited immediate loading of RNAPII at activated promoters, followed by increases in pause-release5, while repressed promoters showed opposite effects. Gains and losses in RNAPII loading were proportional to the changes in the Myc share, suggesting that repression by Myc may be largely indirect, owing - at least in part - to competition for limiting amounts of RNAPII. Secondary to the changes in RNAPII loading, the dynamics of elongation and pre-mRNA processing were also rapidly altered at Myc regulated genes, leading to the transient accumulation of partially or aberrantly processed mRNAs. Altogether, our results shed light on how over-expressed Myc alters the various phases of the RNAPII cycle and the resulting transcriptional response.
2017-08-23 | GSE98419 | GEO
Project description:Over-expression of the Myc transcription factor causes its widespread interaction with regulatory domains in the genome, but leads to the up- and down-regulation of discrete sets of genes. The molecular determinants of these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis of transcription and mRNA dynamics following Myc activation in proliferating mouse fibroblasts, based on chromatin immunoprecipitation, metabolic labeling of newly synthesized RNA, extensive sequencing and mathematical modeling. Transcriptional activation correlated with the highest increases in Myc binding at promoters. Repression followed a reciprocal scenario, with the lowest gains in Myc binding. Altogether, the relative abundance (henceforth, “share”) of Myc at promoters was the strongest predictor of transcriptional responses in diverse cell types, predominating over Myc’s association with the co-repressor Miz1. Myc activation elicited immediate loading of RNAPII at activated promoters, followed by increases in pause-release5, while repressed promoters showed opposite effects. Gains and losses in RNAPII loading were proportional to the changes in the Myc share, suggesting that repression by Myc may be largely indirect, owing - at least in part - to competition for limiting amounts of RNAPII. Secondary to the changes in RNAPII loading, the dynamics of elongation and pre-mRNA processing were also rapidly altered at Myc regulated genes, leading to the transient accumulation of partially or aberrantly processed mRNAs. Altogether, our results shed light on how over-expressed Myc alters the various phases of the RNAPII cycle and the resulting transcriptional response.
2017-08-23 | GSE98418 | GEO