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© Deriano Lab / Institut Pasteur
Chromosomes métaphasiques d’une cellule lymphoïde cancéreuse présentant une amplification des gènes Igh et c-myc
Publication : Nature communications

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature communications - 01 Dec 2021

Robert-Finestra T, Tan BF, Mira-Bontenbal H, Timmers E, Gontan C, Merzouk S, Giaimo BD, Dossin F, van IJcken WFJ, Martens JWM, Borggrefe T, Heard E, Gribnau J,

Link to Pubmed [PMID] – 34853312

Link to DOI – 10.1038/s41467-021-27294-5

Nat Commun 2021 Dec; 12(1): 7000

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.

https://pubmed.ncbi.nlm.nih.gov/34853312