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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 et al_2021.pdf (Verlagsversion), 859KB
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Enervald, Elin , Autor
Powell, Lynn Marie , Autor
Boteva, Lora , Autor
Foti, Rossana , Autor
Ruiz, Nerea Blanes , Autor
Kibar, Gözde1, Autor           
Piszczek, Agnieszka , Autor
Cavaleri, Fatima , Autor
Vingron, Martin1, Autor           
Cerase, Andrea , Autor
Buonomo, Sara B. C. , Autor
Affiliations:
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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 Zusammenfassung: 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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Sprache(n): eng - English
 Datum: 2021-10-192021-11-17
 Publikationsstatus: Online veröffentlicht
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 Identifikatoren: DOI: 10.15252/embj.2020105862
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Titel: The EMBO Journal
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Nature Publishing Group
Seiten: - Band / Heft: 40 Artikelnummer: e105862 Start- / Endseite: - Identifikator: ISSN: 0261-4189
CoNE: https://pure.mpg.de/cone/journals/resource/954925497061_1