Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
Publ. Version/Full Text
DOI
PMC
 |
Open Access Gold (Paid Option) |
|
as soon as is submitted to ZB.
Distal and proximal cis-regulatory elements sense X chromosome dosage and developmental state at the Xist locus.
Mol. Cell 82, 190-208.e17 (2021)
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.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Crispr Screens ; Crispri ; X-chromosome Inactivation ; Xert ; Xist ; Chromatin Modifications ; Enhancers ; Epigenetics ; Lncrna; Gene-expression; Read Alignment; Noncoding Rna; Transcription Factors; Inactivation Center; Reveals Principles; Tsix Transcription; Human Genome; In-vitro; Chromatin
ISSN (print) / ISBN
1097-2765
e-ISSN
1097-4164
Journal
Molecular Cell
Quellenangaben
Volume: 82,
Issue: 1,
Pages: 190-208.e17
Publisher
Elsevier
Publishing Place
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Computational Biology (ICB)
Grants
E:bio Module III-Xnet grant
Wellcome Trust
DFG
Deutsche Forschungsgemeinschaft (DFG)
Human Frontiers Science Program
Max-Planck Research Group Leader program
Wellcome Trust
DFG
Deutsche Forschungsgemeinschaft (DFG)
Human Frontiers Science Program
Max-Planck Research Group Leader program