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| Item Type: | Article |
|---|---|
| Title: | Distal and proximal cis-regulatory elements sense X chromosome dosage and developmental state at the Xist locus |
| Creators Name: | Gjaltema, R.A.F., Schwämmle, T., Kautz, P., Robson, M., Schöpflin, R., Ravid Lustig, L., Brandenburg, L., Dunkel, I., Vechiatto, C., Ntini, E., Mutzel, V., Schmiedel, V., Marsico, A., Mundlos, S. and Schulz, E.G. |
| Abstract: | Developmental genes such as Xist, which initiates X chromosome inactivation, are controlled by complex cis-regulatory landscapes, which decode multiple signals to establish specific spatiotemporal expression patterns. Xist integrates information on X chromosome dosage and developmental stage to trigger X inactivation in the epiblast specifically in female embryos. Through a pooled CRISPR screen in differentiating mouse embryonic stem cells, we identify functional enhancer elements of Xist at the onset of random X inactivation. Chromatin profiling reveals that X-dosage controls the promoter-proximal region, while differentiation cues activate several distal enhancers. The strongest distal element lies in an enhancer cluster associated with a previously unannotated Xist-enhancing regulatory transcript, which we named Xert. Developmental cues and X-dosage are thus decoded by distinct regulatory regions, which cooperate to ensure female-specific Xist upregulation at the correct developmental time. With this study, we start to disentangle how multiple, functionally distinct regulatory elements interact to generate complex expression patterns in mammals. |
| Keywords: | X-Chromosome Inactivation, Xist, CRISPR Screens, Enhancers, lncRNA, Xert, Chromatin Modifications, Epigenetics, CRISPRi, Animals, Mice |
| Source: | Molecular Cell |
| ISSN: | 1097-2765 |
| Publisher: | Cell Press |
| Volume: | 82 |
| Number: | 1 |
| Page Range: | 190-208.e17 |
| Date: | 6 January 2022 |
| Official Publication: | https://doi.org/10.1016/j.molcel.2021.11.023 |
| PubMed: | View item in PubMed |
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