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SPEN is required for Xist upregulation during initiation of X chromosome inactivation

At initiation of X chromosome inactivation (XCI), Xist is monoallelically upregulated from the future inactive X (Xi) chromosome, overcoming repression by its antisense transcript Tsix. Xist recruits various chromatin remodelers, amongst them SPEN, which are involved in silencing of X-linked genes i...

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Autores principales: Robert-Finestra, Teresa, Tan, Beatrice F., Mira-Bontenbal, Hegias, Timmers, Erika, Gontan, Cristina, Merzouk, Sarra, Giaimo, Benedetto Daniele, Dossin, François, van IJcken, Wilfred F. J., Martens, John W. M., Borggrefe, Tilman, Heard, Edith, Gribnau, Joost
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636516/
https://www.ncbi.nlm.nih.gov/pubmed/34853312
http://dx.doi.org/10.1038/s41467-021-27294-5
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author Robert-Finestra, Teresa
Tan, Beatrice F.
Mira-Bontenbal, Hegias
Timmers, Erika
Gontan, Cristina
Merzouk, Sarra
Giaimo, Benedetto Daniele
Dossin, François
van IJcken, Wilfred F. J.
Martens, John W. M.
Borggrefe, Tilman
Heard, Edith
Gribnau, Joost
author_facet Robert-Finestra, Teresa
Tan, Beatrice F.
Mira-Bontenbal, Hegias
Timmers, Erika
Gontan, Cristina
Merzouk, Sarra
Giaimo, Benedetto Daniele
Dossin, François
van IJcken, Wilfred F. J.
Martens, John W. M.
Borggrefe, Tilman
Heard, Edith
Gribnau, Joost
author_sort Robert-Finestra, Teresa
collection PubMed
description At initiation of X chromosome inactivation (XCI), Xist is monoallelically upregulated from the future inactive X (Xi) chromosome, overcoming repression by its antisense transcript Tsix. Xist recruits various chromatin remodelers, amongst them SPEN, which are involved in silencing of X-linked genes in cis and establishment of the Xi. Here, we show that SPEN plays an important role in initiation of XCI. Spen null female mouse embryonic stem cells (ESCs) are defective in Xist upregulation upon differentiation. We find that Xist-mediated SPEN recruitment to the Xi chromosome happens very early in XCI, and that SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation. Accordingly, failed Xist upregulation in Spen(−/−) ESCs can be rescued by concomitant removal of Tsix. These findings indicate that SPEN is not only required for the establishment of the Xi, but is also crucial in initiation of the XCI process.
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spelling pubmed-86365162021-12-15 SPEN is required for Xist upregulation during initiation of X chromosome inactivation Robert-Finestra, Teresa Tan, Beatrice F. Mira-Bontenbal, Hegias Timmers, Erika Gontan, Cristina Merzouk, Sarra Giaimo, Benedetto Daniele Dossin, François van IJcken, Wilfred F. J. Martens, John W. M. Borggrefe, Tilman Heard, Edith Gribnau, Joost Nat Commun Article At initiation of X chromosome inactivation (XCI), Xist is monoallelically upregulated from the future inactive X (Xi) chromosome, overcoming repression by its antisense transcript Tsix. Xist recruits various chromatin remodelers, amongst them SPEN, which are involved in silencing of X-linked genes in cis and establishment of the Xi. Here, we show that SPEN plays an important role in initiation of XCI. Spen null female mouse embryonic stem cells (ESCs) are defective in Xist upregulation upon differentiation. We find that Xist-mediated SPEN recruitment to the Xi chromosome happens very early in XCI, and that SPEN-mediated silencing of the Tsix promoter is required for Xist upregulation. Accordingly, failed Xist upregulation in Spen(−/−) ESCs can be rescued by concomitant removal of Tsix. These findings indicate that SPEN is not only required for the establishment of the Xi, but is also crucial in initiation of the XCI process. Nature Publishing Group UK 2021-12-01 /pmc/articles/PMC8636516/ /pubmed/34853312 http://dx.doi.org/10.1038/s41467-021-27294-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Robert-Finestra, Teresa
Tan, Beatrice F.
Mira-Bontenbal, Hegias
Timmers, Erika
Gontan, Cristina
Merzouk, Sarra
Giaimo, Benedetto Daniele
Dossin, François
van IJcken, Wilfred F. J.
Martens, John W. M.
Borggrefe, Tilman
Heard, Edith
Gribnau, Joost
SPEN is required for Xist upregulation during initiation of X chromosome inactivation
title SPEN is required for Xist upregulation during initiation of X chromosome inactivation
title_full SPEN is required for Xist upregulation during initiation of X chromosome inactivation
title_fullStr SPEN is required for Xist upregulation during initiation of X chromosome inactivation
title_full_unstemmed SPEN is required for Xist upregulation during initiation of X chromosome inactivation
title_short SPEN is required for Xist upregulation during initiation of X chromosome inactivation
title_sort spen is required for xist upregulation during initiation of x chromosome inactivation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636516/
https://www.ncbi.nlm.nih.gov/pubmed/34853312
http://dx.doi.org/10.1038/s41467-021-27294-5
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