TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control
| العنوان: | TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control |
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| المؤلفون: | Jane L. Wagstaff, James C Williamson, Paul J. Lehner, Yorgo Modis, Stefan M.V. Freund, Marta Seczynska, Iva A. Tchasovnikarova, Richard T. Timms, Christopher H. Douse, Anna V. Protasio, Daniil M. Prigozhin, Anna Albecka |
| المساهمون: | Douse, Christopher H. [0000-0002-1604-8944], Timms, Richard T. [0000-0001-7275-597X], Protasio, Anna V. [0000-0003-1723-800X], Prigozhin, Daniil M. [0000-0003-2075-0231], Lehner, Paul J. [0000-0001-9383-1054], Modis, Yorgo [0000-0002-6084-0429], Apollo - University of Cambridge Repository, Douse, Christopher H [0000-0002-1604-8944], Timms, Richard T [0000-0001-7275-597X], Protasio, Anna V [0000-0003-1723-800X], Prigozhin, Daniil M [0000-0003-2075-0231], Lehner, Paul J [0000-0001-9383-1054] |
| المصدر: | Nature communications, vol 11, iss 1 Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Nature Communications |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, 82/29, Magnetic Resonance Spectroscopy, Transcription, Genetic, Transcriptional regulatory elements, 631/337/572/2102, Post-Transcriptional, General Physics and Astronomy, Epigenesis, Genetic, Histones, 631/337/176/2016, 13/1, 0302 clinical medicine, Transcription (biology), Histone post-translational modifications, Transcriptional regulation, RNA Processing, Post-Transcriptional, lcsh:Science, Epigenomics, 0303 health sciences, Multidisciplinary, Genome, article, Gene silencing, Nuclear Proteins, Exons, Chromatin immunoprecipitation, 96/63, Cell biology, Chromatin, 13/31, 631/337/100/2285, 82/6, Poly(ADP-ribose) Polymerases, Transcription, Protein Binding, Transposable element, RNA Processing, Architecture domain, 145, 1.1 Normal biological development and functioning, Science, Protein domain, 101/58, Computational biology, Biology, Methylation, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Genetic, Protein Domains, Underpinning research, Antigens, Neoplasm, Genetics, Humans, Epigenetics, Amino Acid Sequence, Antigens, 82/83, Gene, Psychological repression, 030304 developmental biology, X-ray crystallography, 45/91, Binding Sites, 82/16, 030102 biochemistry & molecular biology, Lysine, Human Genome, RNA, General Chemistry, 45/15, NAD, Phosphoproteins, 42/35, 030104 developmental biology, HEK293 Cells, 631/1647/2217/2088, 631/535/1266, Hela Cells, Multiprotein Complexes, DNA Transposable Elements, Neoplasm, lcsh:Q, Generic health relevance, 030217 neurology & neurosurgery, Epigenesis, HeLa Cells |
| الوصف: | The HUSH complex represses retroviruses, transposons and genes to maintain the integrity of vertebrate genomes. HUSH regulates deposition of the epigenetic mark H3K9me3, but how its three core subunits — TASOR, MPP8 and Periphilin — contribute to assembly and targeting of the complex remains unknown. Here, we define the biochemical basis of HUSH assembly and find that its modular architecture resembles the yeast RNA-induced transcriptional silencing complex. TASOR, the central HUSH subunit, associates with RNA processing components. TASOR is required for H3K9me3 deposition over LINE-1 repeats and repetitive exons in transcribed genes. In the context of previous studies, this suggests that an RNA intermediate is important for HUSH activity. We dissect the TASOR and MPP8 domains necessary for transgene repression. Structure-function analyses reveal TASOR bears a catalytically-inactive PARP domain necessary for targeted H3K9me3 deposition. We conclude that TASOR is a multifunctional pseudo-PARP that directs HUSH assembly and epigenetic regulation of repetitive genomic targets. The HUSH complex plays a key role in controlling transcription of viruses and transposable elements. Here, the authors define the biochemical basis of HUSH assembly and show that the TASOR subunit contains a pseudo-PARP domain critical for HUSH-dependent transgene repression and H3K9me3 deposition over targets genome wide. |
| وصف الملف: | application/pdf; application/zip; text/xml |
| DOI: | 10.17863/cam.57347 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3fc12be48169780201fb05f42ca82ce8 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3fc12be48169780201fb05f42ca82ce8 |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.17863/cam.57347 |
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