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TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control

Douse, Christopher H. LU ; Tchasovnikarova, Iva A. ; Timms, Richard T. ; Protasio, Anna V. ; Seczynska, Marta ; Prigozhin, Daniil M. ; Albecka, Anna ; Wagstaff, Jane ; Williamson, James C. and Freund, Stefan M.V. , et al. (2020) In Nature Communications 11(1).
Abstract

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... (More)

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.

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publication status
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subject
in
Nature Communications
volume
11
issue
1
article number
4940
publisher
Nature Publishing Group
external identifiers
  • pmid:33009411
  • scopus:85091890227
ISSN
2041-1723
DOI
10.1038/s41467-020-18761-6
language
English
LU publication?
yes
id
2f48ebda-c110-482b-8274-1d7914c014d1
date added to LUP
2021-01-07 13:41:32
date last changed
2024-04-03 18:46:09
@article{2f48ebda-c110-482b-8274-1d7914c014d1,
  abstract     = {{<p>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.</p>}},
  author       = {{Douse, Christopher H. and Tchasovnikarova, Iva A. and Timms, Richard T. and Protasio, Anna V. and Seczynska, Marta and Prigozhin, Daniil M. and Albecka, Anna and Wagstaff, Jane and Williamson, James C. and Freund, Stefan M.V. and Lehner, Paul J. and Modis, Yorgo}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{TASOR is a pseudo-PARP that directs HUSH complex assembly and epigenetic transposon control}},
  url          = {{http://dx.doi.org/10.1038/s41467-020-18761-6}},
  doi          = {{10.1038/s41467-020-18761-6}},
  volume       = {{11}},
  year         = {{2020}},
}