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Co-transcriptional genome surveillance by HUSH is coupled to termination (CLIP-Seq)

ABSTRACT: Co-transcriptional genome surveillance by HUSH is coupled to termination (CLIP-Seq)

PROVIDER: PRJNA860949 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20576835.fastq.gz	Fastqsanger.gz
	SRR20576836.fastq.gz	Fastqsanger.gz

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Co-transcriptional genome surveillance by HUSH is coupled to termination (CLIP-Seq)

Project description:The HUSH complex recognizes and silences foreign DNA such as viruses, transposons, and transgenes without prior exposure to its targets. Recent studies revealed that HUSH recruitment is dependent on transcription, but a unifying molecular mechanism by which HUSH identifies its targets as ‘non-self’ DNA and selects them for silencing remains unknown. Harnessing a de novo silencing event in ESCs, we uncover distinct modes of HUSH function – one involves co-transcriptional surveillance in the absence of silencing, while the other is associated with H3K9me3 deposition and repression. We demonstrate that HUSH travels with elongating RNAPII, interacts with the transcriptional termination machinery, and accumulates on chromatin in a manner dependent on the termination factor WDR82. We further show that perturbation of endogenous termination signals triggers the switch from HUSH surveillance to silencing. Together, our results uncover an RNAi-independent, co-transcriptional gene silencing mechanism in mammals that senses aberrant termination to distinguish self from non-self.

2023-05-09 | GSE208751 | GEO

Co-transcriptional genome surveillance by HUSH is coupled to termination (PRO-Seq)

2023-05-09 | GSE208752 | GEO

Co-transcriptional genome surveillance by HUSH is coupled to termination (RNA-Seq)

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Co-transcriptional genome surveillance by HUSH is coupled to termination (ChIP-Seq)

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Co-transcriptional genome surveillance by HUSH is coupled to termination

Project description:Co-transcriptional genome surveillance by HUSH is coupled to termination

| PRJNA860944 | ENA

Co-transcriptional genome surveillance by HUSH is coupled to termination (RNA-Seq)

Project description:Co-transcriptional genome surveillance by HUSH is coupled to termination (RNA-Seq)

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Co-transcriptional genome surveillance by HUSH is coupled to termination (PRO-Seq)

Project description:Co-transcriptional genome surveillance by HUSH is coupled to termination (PRO-Seq)

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Co-transcriptional genome surveillance by HUSH is coupled to termination (ChIP-Seq)

Project description:Co-transcriptional genome surveillance by HUSH is coupled to termination (ChIP-Seq)

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Co-transcriptional genome surveillance by HUSH is coupled to termination

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-09 | GSE208753 | GEO

Genome surveillance through repression of intronless mobile elements by the HUSH complex

Project description:All life forms defend their genome against DNA invasion. Eukaryotic cells recognize incoming DNA and limit transcription through repressive chromatin modifications. The human silencing hub (HUSH) complex transcriptionally represses long interspersed element-1 retrotransposons (L1s) and retroviruses through histone H3 Lys9 trimethylation (H3K9me3). How HUSH recognizes and initiates silencing of these invading genetic elements is unknown. Here, we show that HUSH is able to recognize and transcriptionally repress a broad range of long, intronless transgenes. Intron insertion into HUSH-repressed transgenes counteracts repression, even in the absence of intron splicing. HUSH binds transcripts from the target locus, prior to and independent of H3K9me3 deposition, and target transcription is essential for both initiation and propagation of HUSH-mediated H3K9me3. Genomic data reveals how HUSH binds and represses a subset of endogenous intronless genes generated through retrotransposition of cellular mRNAs. Therefore, intronless cDNA, a hallmark of reverse transcription, provides a versatile means to distinguish invading retroelements from host genes and allows HUSH to protect the genome from ‘non-self’ DNA, despite no prior exposure to the invading element. Our findings reveal the existence of a genome surveillance system and explain how it provides immediate protection against newly acquired elements while avoiding inappropriate repression of host genes.

2021-09-30 | GSE181113 | GEO

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