Distal and proximal cis-regulatory elements sense X chromosome dosage and developmental state at the Xist locus.
Mol Cell
; 82(1): 190-208.e17, 2022 01 06.
Article
en En
| MEDLINE
| ID: mdl-34932975
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cromosoma X
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Elementos de Facilitación Genéticos
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Regiones Promotoras Genéticas
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Inactivación del Cromosoma X
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Sitios Genéticos
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ARN Largo no Codificante
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Células Madre Embrionarias de Ratones
Límite:
Animals
Idioma:
En
Revista:
Mol Cell
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania