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INTAC endonuclease and phosphatase modules have distinct roles in transcription (TT-Seq)

ABSTRACT: INTAC endonuclease and phosphatase modules have distinct roles in transcription (TT-Seq)

PROVIDER: PRJNA925496 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23125359_1.fastq.gz	Fastqsanger.gz
	SRR23125359_2.fastq.gz	Fastqsanger.gz
	SRR23125360_1.fastq.gz	Fastqsanger.gz
	SRR23125360_2.fastq.gz	Fastqsanger.gz
	SRR23125361_1.fastq.gz	Fastqsanger.gz

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INTAC endonuclease and phosphatase modules have distinct roles in transcription (TT-Seq)

Project description:Gene expression in metazoans is controlled by promoter-proximal pausing of RNA polymerase II, which can undergo productive elongation or early termination. Integrator-PP2A (INTAC) plays a crucial role in determining the fate of paused polymerases, but the underlying mechanisms remain unclear. Here we establish a rapid degradation system to dissect the direct functions of INTAC RNA endonuclease and phosphatase modules. We find that both catalytic modules function at most if not all active promoters and enhancers, yet differentially affect polymerase fate. The endonuclease module induces early termination, with its disruption leading to accumulation of non-competent polymerases and downregulation of highly expressed genes, while competent polymerases accumulate at lowly expressed genes and non- coding elements, leading to their upregulation. The phosphatase module primarily prevents the release of paused polymerases and limits transcriptional activation, especially for highly paused genes. Thus both INTAC’s catalytic modules have unexpectedly general yet distinct roles in dynamic transcriptional control. We performed PRO-seq, ChIP-seq, or TT-seq to investigate the role of INTAC in regulating transcription.

2023-04-19 | GSE223264 | GEO

INTAC endonuclease and phosphatase modules have distinct roles in transcription (PRO-Seq)

2023-04-19 | GSE223260 | GEO

INTAC endonuclease and phosphatase modules have distinct roles in transcription (ChP-Seq)

2023-04-19 | GSE223252 | GEO

INTAC endonuclease and phosphatase modules differentially regulate transcription by RNA polymerase II

Project description:Gene expression in metazoans is controlled by promoter-proximal pausing of RNA polymerase II, which can undergo productive elongation or early termination. Integrator-PP2A (INTAC) plays a crucial role in determining the fate of paused polymerases, but the underlying mechanisms remain unclear. Here we establish a rapid degradation system to dissect the direct functions of INTAC RNA endonuclease and phosphatase modules. We find that both catalytic modules function at most if not all active promoters and enhancers, yet differentially affect polymerase fate. The endonuclease module induces early termination, with its disruption leading to accumulation of non-competent polymerases and downregulation of highly expressed genes, while competent polymerases accumulate at lowly expressed genes and non- coding elements, leading to their upregulation. The phosphatase module primarily prevents the release of paused polymerases and limits transcriptional activation, especially for highly paused genes. Thus both INTAC’s catalytic modules have unexpectedly general yet distinct roles in dynamic transcriptional control. This SuperSeries is composed of the SubSeries listed below.

2023-04-19 | GSE223265 | GEO

INTAC endonuclease and phosphatase modules have distinct roles in transcription (PRO-Seq)

Project description:INTAC endonuclease and phosphatase modules have distinct roles in transcription (PRO-Seq)

| PRJNA925662 | ENA

INTAC endonuclease and phosphatase modules have distinct roles in transcription (ChP-Seq)

Project description:INTAC endonuclease and phosphatase modules have distinct roles in transcription (ChP-Seq)

| PRJNA925664 | ENA

INTAC endonuclease and phosphatase modules differentially regulate transcription by RNA polymerase II

Project description:INTAC endonuclease and phosphatase modules differentially regulate transcription by RNA polymerase II

| PRJNA925487 | ENA

Integrator endonuclease drives promoter-proximal termination at all RNAPII transcribed loci (TT-seq)

Project description:Pausing of RNA polymerase II (RNAPII) in early elongation is critical for gene regulation. Paused RNAPII can be released into productive elongation by the kinase P-TEFb or targeted for premature termination by the Integrator complex. Integrator comprises endonuclease and phosphatase activities, driving termination through cleavage of nascent RNA and removal of stimulatory phosphorylation. To probe the direct consequences of Integrator activity, we generated a degron system to rapidly deplete the Integrator endonuclease INTS11. Degradation of INTS11 elicits a nearly universal increase in RNAPII escape from promoter regions. However, these RNAPII complexes fail to achieve optimal elongation rates and reveal continued Integrator phosphatase activity. Short transcripts are thus selectively upregulated by INTS11 loss, including many non-coding RNAs, transcription factors and signaling regulators. Together, our data indicate a common function for INTS11 at all RNAPII loci, with differential effects on particular genes, pathways or RNA biotypes reflecting transcript lengths rather than Integrator specificity.

2022-10-28 | GSE200701 | GEO

Integrator endonuclease drives promoter-proximal termination at all RNAPII transcribed loci (TT-seq)

Project description:Integrator endonuclease drives promoter-proximal termination at all RNAPII transcribed loci (TT-seq)

| PRJNA826099 | ENA

Project description:tt

| PRJEB51254 | ENA