Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
A hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional react...
| Autores: | ; ; ; ; ; ; |
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| Tipo de documento: | Artigo |
| Estado: | Published version |
| Data de publicação: | 2021 |
| País: | España |
| Recursos: | Universitat Pompeu Fabra |
| Repositório: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/49045 |
| Acesso em linha: | http://hdl.handle.net/10230/49045 http://dx.doi.org/10.1038/s41467-021-23610-1 |
| Nível de acesso: | Acesso aberto |
| Palavra-chave: | Chromatin structure Dosage compensation Epigenetics Epigenomics Reprogramming |
| Resumo: | A hallmark of chromosome organization is the partition into transcriptionally active A and repressed B compartments, and into topologically associating domains (TADs). Both structures were regarded to be absent from the inactive mouse X chromosome, but to be re-established with transcriptional reactivation and chromatin opening during X-reactivation. Here, we combine a tailor-made mouse iPSC reprogramming system and high-resolution Hi-C to produce a time course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we observe A/B-like compartments on the inactive X harbouring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, concomitant with downregulation of Xist. Importantly, we find that TAD formation precedes transcription and initiates from Xist-poor compartments. Here, we show that TAD formation and transcriptional reactivation are causally independent during X-reactivation while establishing Xist as a common denominator. |
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