| Autor: |
Vallot, C, Patrat, C, Collier, AJ, Huret, C, Casanova, M, Liyakat Ali, TM, Tosolini, M, Frydman, N, Heard, E, Rugg-Gunn, PJ, Rougeulle, C |
| Přispěvatelé: |
Rugg-Gunn, Peter [0000-0002-9601-5949], Apollo - University of Cambridge Repository |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| DOI: |
10.17863/cam.6995 |
| Popis: |
Sex chromosome dosage compensation is essential in most metazoans, but the developmental timing and underlying mechanisms vary significantly, even among placental mammals. Here we identify human-specific mechanisms regulating X chromosome activity in early embryonic development. Single-cell RNA sequencing and imaging revealed co-activation and accumulation of the long noncoding RNAs (lncRNAs) $\textit{XACT}$ and $\textit{XIST}$ on active X chromosomes in both early human pre-implantation embryos and naive human embryonic stem cells. In these contexts, the $\textit{XIST}$ RNA adopts an unusual, highly dispersed organization, which may explain why it does not trigger X chromosome inactivation at this stage. Functional studies in transgenic mouse cells show that $\textit{XACT}$ influences $\textit{XIST}$ accumulation in $\textit{cis}$. Our findings therefore suggest a mechanism involving antagonistic activity of $\textit{XIST}$ and $\textit{XACT}$ in controlling X chromosome activity in early human embryos, and they highlight the contribution of rapidly evolving lncRNAs to species-specific developmental mechanisms. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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