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Mus musculus

ABSTRACT: Transcription of mammalian cis-regulatory elements is restrained by actively enforced early termination [ChIP-Seq]

PROVIDER: PRJNA278458 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1916900.fastq.gz	Fastqsanger.gz
	SRR1916910.fastq.gz	Fastqsanger.gz
	SRR1916901.fastq.gz	Fastqsanger.gz
	SRR1916911.fastq.gz	Fastqsanger.gz
	SRR1916902.fastq.gz	Fastqsanger.gz

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Transcription of mammalian cis-regulatory elements is restrained by actively enforced early termination

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Restrictor synergizes with Symplekin and PNUTS to terminate extragenic transcription

Project description:Transcription termination pathways mitigate the detrimental consequences of unscheduled promiscuous initiation occurring at hundreds of thousands of genomic cis-regulatory elements. The Restrictor complex, composed of the Pol II-interacting protein WDR82 and the RNA-binding protein ZC3H4, suppresses processive transcription at thousands of extragenic sites in mammalian genomes. Restrictor-driven termination does not involve nascent RNA cleavage and its interplay with other termination machineries is unclear. Here we show that efficient termination at Restrictor-controlled extragenic transcription units involves the recruitment of the protein phosphatase 1 (PP1) regulatory subunit PNUTS, a negative regulator of the Spt5 elongation factor, and Symplekin, a protein associated with RNA cleavage complexes but also involved in cleavage-independent and phosphatase-dependent termination of non-coding RNAs in yeast. PNUTS and Symplekin act synergistically with, but independently from Restrictor to dampen processive extragenic transcription. Moreover, the presence of limiting nuclear levels of Symplekin imposes a competition for its recruitment among multiple transcription termination machineries, resulting in mutual regulatory interactions. Hence, by synergizing with Restrictor, Symplekin and PNUTS enable efficient termination of processive, long-range extragenic transcription.

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Transcription of mammalian cis-regulatory elements is restrained by actively enforced early termination [Hi-C]

Project description:Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol_II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adapter protein WDR82 and its associated complexes actively limit such non-coding transcription. WDR82 targets the SET1/COMPASS H3K4 methyltransferase and the nuclear Protein Phosphatase 1 (PP1) complexes to the initiating Pol_II. WDR82 and PP1 also interact with components of the transcriptional termination and RNA processing machineries. Depletion of WDR82, SET1 or the PP1 subunit required for its nuclear import caused distinct but overlapping transcription termination defects at highly expressed genes, active enhancers and promoters, thus enabling the increased synthesis of unusually long ncRNAs. These data indicate that transcription initiated from cis-regulatory elements is tightly coordinated with termination mechanisms that impose the synthesis of short RNAs. Hi-C experiments on biological replicates of BMDMs

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Transcription of mammalian cis-regulatory elements is restrained by actively enforced early termination [4C]

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