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  RIF1 and KAP1 differentially regulate the choice of inactive versus active X chromosomes

Enervald, E., Powell, L. M., Boteva, L., Foti, R., Ruiz, N. B., Kibar, G., et al. (2021). RIF1 and KAP1 differentially regulate the choice of inactive versus active X chromosomes. The EMBO Journal, 40: e105862. doi:10.15252/embj.2020105862.

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Enervald, Elin , Author
Powell, Lynn Marie , Author
Boteva, Lora , Author
Foti, Rossana , Author
Ruiz, Nerea Blanes , Author
Kibar, Gözde1, Author              
Piszczek, Agnieszka , Author
Cavaleri, Fatima , Author
Vingron, Martin1, Author              
Cerase, Andrea , Author
Buonomo, Sara B. C. , Author
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1Transcriptional Regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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 Abstract: The onset of random X chromosome inactivation in mouse requires the switch from a symmetric to an asymmetric state, where the identities of the future inactive and active X chromosomes are assigned. This process is known as X chromosome choice. Here, we show that RIF1 and KAP1 are two fundamental factors for the definition of this transcriptional asymmetry. We found that at the onset of differentiation of mouse embryonic stem cells (mESCs), biallelic up-regulation of the long non-coding RNA Tsix weakens the symmetric association of RIF1 with the Xist promoter. The Xist allele maintaining the association with RIF1 goes on to up-regulate Xist RNA expression in a RIF1-dependent manner. Conversely, the promoter that loses RIF1 gains binding of KAP1, and KAP1 is required for the increase in Tsix levels preceding the choice. We propose that the mutual exclusion of Tsix and RIF1, and of RIF1 and KAP1, at the Xist promoters establish a self-sustaining loop that transforms an initially stochastic event into a stably inherited asymmetric X-chromosome state.

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Language(s): eng - English
 Dates: 2021-10-192021-11-17
 Publication Status: Published online
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 Identifiers: DOI: 10.15252/embj.2020105862
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Title: The EMBO Journal
Source Genre: Journal
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Publ. Info: Nature Publishing Group
Pages: - Volume / Issue: 40 Sequence Number: e105862 Start / End Page: - Identifier: ISSN: 0261-4189
CoNE: https://pure.mpg.de/cone/journals/resource/954925497061_1