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- Title
Chd8 regulates X chromosome inactivation in mouse through fine-tuning control of Xist expression.
- Authors
Cerase, Andrea; Young, Alexander N.; Ruiz, Nerea Blanes; Buness, Andreas; Sant, Gabrielle M.; Arnold, Mirjam; Di Giacomo, Monica; Ascolani, Michela; Kumar, Manish; Hierholzer, Andreas; Trigiante, Giuseppe; Marzi, Sarah J.; Avner, Philip
- Abstract
Female mammals achieve dosage compensation by inactivating one of their two X chromosomes during development, a process entirely dependent on Xist, an X-linked long non-coding RNA (lncRNA). At the onset of X chromosome inactivation (XCI), Xist is up-regulated and spreads along the future inactive X chromosome. Contextually, it recruits repressive histone and DNA modifiers that transcriptionally silence the X chromosome. Xist regulation is tightly coupled to differentiation and its expression is under the control of both pluripotency and epigenetic factors. Recent evidence has suggested that chromatin remodelers accumulate at the X Inactivation Center (XIC) and here we demonstrate a new role for Chd8 in Xist regulation in differentiating ES cells, linked to its control and prevention of spurious transcription factor interactions occurring within Xist regulatory regions. Our findings have a broader relevance, in the context of complex, developmentally-regulated gene expression. Andrea Cerase et al. report that the chromatin remodeler Chd8 is a key regulator of mammalian Xist expression and therefore X chromosome inactivation. They find that Chd8 activates Xist expression in embryonic stem cells, while in differentiating cells it acts to prevent spurious Xist expression through blocking transcription factor binding to the Xist promoter.
- Subjects
X chromosome; NON-coding RNA; TRANSCRIPTION factors; PROMOTERS (Genetics); EMBRYONIC stem cells
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-01945-1