2021/04/15 by Andrea Cerase, Alexander N. Young, Nerea Ruiz +10 · 1 citation
Biochemistry, Genetics and Molecular Biology · #Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities #Cancer-related molecular mechanisms research #Genomics and Chromatin Dynamics
paper · pdf · doi:10.1038/s42003-021-01945-1
openalex publication_date 2021/04/15 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/23
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.