Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

KAP1 negatively regulates elongation kinetics to activate signal-induced transcription [RNA-Seq]

ABSTRACT: Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction are still unfolding. By combining an acute depletion system with high resolution genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Unexpectedly, acute KAP1 loss triggers an increase in RNA Polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation and dampening IEG transcription. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE266693 | GEO | 2024/05/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

KAP1 negatively regulates elongation kinetics to activate signal-induced transcription [ChIP-Seq]

Project description:Signal-induced transcriptional programs regulate critical biological processes through the precise spatiotemporal activation of Immediate Early Genes (IEGs); however, the mechanisms of transcription induction are still unfolding. By combining an acute depletion system with high resolution genomics approaches to interrogate synchronized, temporal transcription, we reveal that KAP1/TRIM28 is a first responder that fulfills the temporal and heightened transcriptional demand of IEGs. Unexpectedly, acute KAP1 loss triggers an increase in RNA Polymerase II elongation kinetics during early stimulation time points. This elongation defect derails the normal progression through the transcriptional cycle during late stimulation time points, ultimately leading to decreased recruitment of the transcription apparatus for re-initiation and dampening IEG transcription. Collectively, KAP1 plays a counterintuitive role by negatively regulating transcription elongation to support full activation across multiple transcription cycles of genes critical for cell physiology and organismal functions.

2024-05-07 | GSE266691 | GEO

KAP1 negatively regulates elongation kinetics to activate signal-induced transcription [TT-Seq]

2024-05-07 | GSE266694 | GEO

KAP1 negatively regulates elongation kinetics to activate signal-induced transcription [PRO-Seq]

2024-05-07 | GSE266692 | GEO

Activity-assembled nBAF complex mediates rapid immediate early gene transcription by regulating RNA Polymerase II productive elongation

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

Rapid transcription of arc/arg3.1 and other very fast immediate early genes in response to neuronal activity is mediated by a stalled RNA polymerase II mechanism

Project description:Transcription of immediate early genes (IEGs) in neurons is exquisitely sensitive to neuronal activity, but the mechanism underlying the earliest of these transcription events is largely unknown. Here we demonstrate that very fast IEGs (VF-IEGs) such as arc/arg3.1 are poised for rapid transcription by the stalling of RNA Polymerase II (Pol II) just downstream of the transcription start site. RNAi-depletion of two subunits of Negative Elongation Factor, a mediator of Pol II stalling, reduces the Pol II occupancy of the arc promoter and compromises the rapid induction of arc and other VF-IEGs. In contrast, reduction of Pol II stalling did not prevent expression of fast IEGs (F-IEGs). These F-IEGs are expressed with comparatively slower kinetics and largely lack promoter proximal Pol II stalling. Taken together, our data strongly indicate that very fast kinetics of neuronal IEG expression require poised Pol II and suggest a role for this mechanism in transcription-dependent learning and memory. Examination of Pol II bindnig genome-wide in rat neurons

2011-05-24 | E-GEOD-22878 | biostudies-arrayexpress

Neurotoxin tetrodotoxin TTX withdrawal induced neuronal activity: RNA Pol II is poised for rapid induction of arc and other neuronal VF-IEGs

Project description:Transcription of immediate early genes (IEGs) in neurons is exquisitely sensitive to neuronal activity, but the mechanism underlying the earliest of these transcription events is largely unknown. Here we demonstrate that very fast IEGs (VF-IEGs) such as arc/arg3.1 are poised for rapid transcription by the stalling of RNA Polymerase II (Pol II) just downstream of the transcription start site. RNAi-depletion of two subunits of a mediator of Pol II stalling, Negative Elongation Factor, reduces Pol II occupancy of the arc promoter and compromises rapid induction of arc and other VF-IEGs. In contrast, reduction of Pol II stalling did not prevent expression of other fast IEGs (F-IEGs). These F-IEGs are expressed with comparatively slower kinetics and largely lack promoter proximal Pol II stalling. Taken together, our data strongly indicate that very fast kinetics of neuronal IEG expression require poised Pol II and suggest a role for this mechanism in transcription-dependent learning and memory. TTX withdrawal induced neuronal activity. To study activity-induced gene expression, neurons were treated with TTX for 48 hours and then TTX was washed out either for 15 minutes (W15) or for 45 minutes (W45). Gene expression was measured in these two groups in comparison to TTX treated neurons.

2011-04-14 | E-GEOD-22622 | biostudies-arrayexpress

Neurotoxin tetrodotoxin TTX withdrawal induced neuronal activity: RNA Pol II is poised for rapid induction of arc and other neuronal VF-IEGs

Project description:Transcription of immediate early genes (IEGs) in neurons is exquisitely sensitive to neuronal activity, but the mechanism underlying the earliest of these transcription events is largely unknown. Here we demonstrate that very fast IEGs (VF-IEGs) such as arc/arg3.1 are poised for rapid transcription by the stalling of RNA Polymerase II (Pol II) just downstream of the transcription start site. RNAi-depletion of two subunits of a mediator of Pol II stalling, Negative Elongation Factor, reduces Pol II occupancy of the arc promoter and compromises rapid induction of arc and other VF-IEGs. In contrast, reduction of Pol II stalling did not prevent expression of other fast IEGs (F-IEGs). These F-IEGs are expressed with comparatively slower kinetics and largely lack promoter proximal Pol II stalling. Taken together, our data strongly indicate that very fast kinetics of neuronal IEG expression require poised Pol II and suggest a role for this mechanism in transcription-dependent learning and memory.

2011-04-15 | GSE22622 | GEO

Rapid transcription of arc/arg3.1 and other very fast immediate early genes in response to neuronal activity is mediated by a stalled RNA polymerase II mechanism

2011-05-24 | GSE22878 | GEO

KAP1 Recruitment of the 7SK snRNP to Promoters Enables Transcription Elongation by RNA Polymerase II

Project description:The transition from transcription initiation into elongation at promoters of primary response genes (PRG) in metazoan cells is controlled by inducible transcription factors, which utilize P-TEFb to phosphorylate RNA Polymerase II (Pol II) in response to stimuli. Prior to stimulation, a fraction of P-TEFb is recruited to promoters in a catalytically inactive state bound to the 7SK small nuclear ribonucleoprotein (snRNP). However, it remains unclear how and why the 7SK snRNP is assembled at promoters. Here we report that the transcriptional regulator KAP1 directly recruits the 7SK snRNP to facilitate localized release of P-TEFb, promoting rapid Pol II elongation and PRG synthesis in response to stimuli. Collectively, we have discovered and characterized a novel complex, which we term the KEC, which dictates rapid and robust PRG induction upon stimuli.

2015-10-09 | GSE72622 | GEO

Arabidopsis seedlings collected during hypocotyl elongation and hypocotyl stasis

Project description:The hypocotyl of Arabidopsis seedlings shows rhythmic periods of elongation. The patterns of elongation are controlled by a combination of internal factors, such as the circadian clock, and external factors such as light. In a previous study we had found that two transcription factors, PIF4 and PIF5 are important integrators of clock and light signals for the control of elongation. Here we use microarrays to find genes that are correlated with elongation and that are controlled by PIF4 and/or PIF5. Arabidopsis seedlings grown under short day conditions for three days were transferred to SD/3 conditions (160 min light: 320 min dark cycles) from the dawn of the fourth day. Seedlings were then collected during periods of hypocotyl elongation and stasis for three days. There are two types of replication: temporal and independent experiments. For temporal replication, samples collected at the same time of day on subsequent days were used as replicates. In addition, replicate samples were collected in two independent time courses for most time points. Col and CCA1OX samples from the first time course for time points 280, 1240, 1720, 2680, 3160, and 4120 were originally deposited under GEO Series GSE6906; they have been re-analyzed for this study. Each sample consists of multiple pooled seedlings.

2011-03-31 | E-GEOD-21684 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data