Literature DB >> 34813726

Xist nucleates local protein gradients to propagate silencing across the X chromosome.

Yolanda Markaki1, Johnny Gan Chong2, Yuying Wang2, Elsie C Jacobson2, Christy Luong2, Shawn Y X Tan2, Joanna W Jachowicz3, Mackenzie Strehle3, Davide Maestrini4, Abhik K Banerjee3, Bhaven A Mistry5, Iris Dror2, Francois Dossin6, Johannes Schöneberg7, Edith Heard6, Mitchell Guttman3, Tom Chou8, Kathrin Plath9.   

Abstract

The lncRNA Xist forms ∼50 diffraction-limited foci to transcriptionally silence one X chromosome. How this small number of RNA foci and interacting proteins regulate a much larger number of X-linked genes is unknown. We show that Xist foci are locally confined, contain ∼2 RNA molecules, and nucleate supramolecular complexes (SMACs) that include many copies of the critical silencing protein SPEN. Aggregation and exchange of SMAC proteins generate local protein gradients that regulate broad, proximal chromatin regions. Partitioning of numerous SPEN molecules into SMACs is mediated by their intrinsically disordered regions and essential for transcriptional repression. Polycomb deposition via SMACs induces chromatin compaction and the increase in SMACs density around genes, which propagates silencing across the X chromosome. Our findings introduce a mechanism for functional nuclear compartmentalization whereby crowding of transcriptional and architectural regulators enables the silencing of many target genes by few RNA molecules.
Copyright © 2021 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  RNA-binding proteins; X chromosome inactivation; Xist RNA; biomolecular condensates; chromatin organization; heterochromatin; macromolecular dynamics; quantitative imaging; super-resolution microscopy; supramolecular complexes

Mesh:

Substances:

Year:  2021        PMID: 34813726      PMCID: PMC8671326          DOI: 10.1016/j.cell.2021.10.022

Source DB:  PubMed          Journal:  Cell        ISSN: 0092-8674            Impact factor:   41.582


  113 in total

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Journal:  Nat Cell Biol       Date:  2010-05-09       Impact factor: 28.824

2.  A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced.

Authors:  Julie Chaumeil; Patricia Le Baccon; Anton Wutz; Edith Heard
Journal:  Genes Dev       Date:  2006-08-15       Impact factor: 11.361

3.  Multicolor 3D fluorescence in situ hybridization for imaging interphase chromosomes.

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4.  Dynamic Organization of Chromatin Domains Revealed by Super-Resolution Live-Cell Imaging.

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Journal:  Mol Cell       Date:  2017-07-14       Impact factor: 17.970

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Authors:  Jean-Yves Tinevez; Nick Perry; Johannes Schindelin; Genevieve M Hoopes; Gregory D Reynolds; Emmanuel Laplantine; Sebastian Y Bednarek; Spencer L Shorte; Kevin W Eliceiri
Journal:  Methods       Date:  2016-10-03       Impact factor: 3.608

6.  Xist Deletional Analysis Reveals an Interdependency between Xist RNA and Polycomb Complexes for Spreading along the Inactive X.

Authors:  David Colognori; Hongjae Sunwoo; Andrea J Kriz; Chen-Yu Wang; Jeannie T Lee
Journal:  Mol Cell       Date:  2019-02-28       Impact factor: 17.970

Review 7.  Gene silencing in X-chromosome inactivation: advances in understanding facultative heterochromatin formation.

Authors:  Anton Wutz
Journal:  Nat Rev Genet       Date:  2011-07-18       Impact factor: 53.242

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Authors:  Curtis T Rueden; Johannes Schindelin; Mark C Hiner; Barry E DeZonia; Alison E Walter; Ellen T Arena; Kevin W Eliceiri
Journal:  BMC Bioinformatics       Date:  2017-11-29       Impact factor: 3.169

Review 9.  Xist RNA in action: Past, present, and future.

Authors:  Agnese Loda; Edith Heard
Journal:  PLoS Genet       Date:  2019-09-19       Impact factor: 5.917

10.  SPEN integrates transcriptional and epigenetic control of X-inactivation.

Authors:  Inês Pinheiro; Jan J Żylicz; François Dossin; Julia Roensch; Samuel Collombet; Agnès Le Saux; Tomasz Chelmicki; Mikaël Attia; Varun Kapoor; Ye Zhan; Florent Dingli; Damarys Loew; Thomas Mercher; Job Dekker; Edith Heard
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Authors:  Elsie C Jacobson; Amy Pandya-Jones; Kathrin Plath
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4.  Xist spatially amplifies SHARP/SPEN recruitment to balance chromosome-wide silencing and specificity to the X chromosome.

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7.  LncRNA RUS shapes the gene expression program towards neurogenesis.

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8.  Phase Separation Drives SARS-CoV-2 Replication: A Hypothesis.

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Review 9.  The tandem repeat modules of Xist lncRNA: a swiss army knife for the control of X-chromosome inactivation.

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Journal:  Biochem Soc Trans       Date:  2021-12-17       Impact factor: 5.407

Review 10.  Long RNA-Mediated Chromatin Regulation in Fission Yeast and Mammals.

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