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Chromosome Compartments on the Inactive X Guide TAD Formation Independently of Transcription during X-Reactivation

By Moritz Bauer, Enrique Vidal, Eduard Zorita, Stefan F. Pinter, Guillaume J. Filion, Bernhard Payer

Posted 03 Jul 2020
bioRxiv DOI: 10.1101/2020.07.02.177790

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 absent from the inactive 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 the first time-course combining gene reactivation, chromatin opening and chromosome topology during X-reactivation. Contrary to previous observations, we uncover A/B-like compartments on the inactive X harboring multiple subcompartments. While partial X-reactivation initiates within a compartment rich in X-inactivation escapees, it then occurs rapidly along the chromosome, coinciding with acquisition of naive pluripotency, leading to downregulation of Xist . Importantly, we find that TAD formation precedes transcription, suggesting them to be causally independent. Instead, TADs form first within Xist-poor compartments, establishing Xist as common denominator, opposing both gene reactivation and TAD formation through separate mechanisms. ![Figure][1]</img> Graphical Summary ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes

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