Evidence map›Paper›PMID 32976585›Full record

ArticleNucleic acids research2020

Periphilin self-association underpins epigenetic silencing by the HUSH complex.

Daniil M Prigozhin, Christopher H Douse, Laura E Farleigh, Anna Albecka, Iva A Tchasovnikarova, Richard T Timms, Shun-Ichiro Oda, Frank Adolf, Stefan M V Freund, Sarah Maslen and 2 more

Abstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Daniil M PrigozhinMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Christopher H DouseMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Laura E FarleighMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Anna AlbeckaMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Iva A TchasovnikarovaCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.
Richard T TimmsCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.
Shun-Ichiro OdaMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Frank AdolfMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Stefan M V FreundNMR Facility, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Sarah MaslenBiological Mass Spectrometry & Proteomics Laboratory, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
Paul J LehnerCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.
Yorgo ModisMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.

Funding

Biotechnology and Biological Sciences Research Council BB/N011791/1Biotechnology and Biological Sciences Research Council MX15916Medical Research Council MC_U105184326Wellcome Trust 101835/Z/13/ZWellcome Trust 101908/Z/13/ZWellcome Trust 201387/Z/16/ZWellcome Trust 210688/Z/18/ZWellcome Trust 217191Wellcome Trust 217191/Z/19/Z
6 · The paper itself

Abstract

Transcription of integrated DNA from viruses or transposable elements is tightly regulated to prevent pathogenesis. The Human Silencing Hub (HUSH), composed of Periphilin, TASOR and MPP8, silences transcriptionally active viral and endogenous transgenes. HUSH recruits effectors that alter the epigenetic landscape and chromatin structure, but how HUSH recognizes target loci and represses their expression remains unclear. We identify the physicochemical properties of Periphilin necessary for HUSH assembly and silencing. A disordered N-terminal domain (NTD) and structured C-terminal domain are essential for silencing. A crystal structure of the Periphilin-TASOR minimal core complex shows Periphilin forms an α-helical homodimer, bound by a single TASOR molecule. The NTD forms insoluble aggregates through an arginine/tyrosine-rich sequence reminiscent of low-complexity regions from self-associating RNA-binding proteins. Residues required for TASOR binding and aggregation were required for HUSH-dependent silencing and genome-wide deposition of repressive mark H3K9me3. The NTD was functionally complemented by low-complexity regions from certain RNA-binding proteins and proteins that form condensates or fibrils. Our work suggests the associative properties of Periphilin promote HUSH aggregation at target loci.

Indexed as

Transcription, GeneticAntigens, NeoplasmCrystallography, X-RayDNA Transposable ElementsEpigenesis, GeneticGene SilencingHumansNuclear ProteinsPhosphoproteinsProtein AggregatesProtein BindingProtein Conformation, alpha-HelicalProtein DomainsRNA-Binding ProteinsVirusesAntigens, NeoplasmDNA Transposable ElementsMPHOSPH8 protein, humanNuclear ProteinsPhosphoproteinsPPHLN1 protein, humanProtein AggregatesRNA-Binding ProteinsTASOR protein, human

Identifiers

PMID32976585
PMCPMC7544229

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.