Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation

Bauer, Moritz, 1987-; Vidal, Enrique; Zorita, Eduard; Üresin, Nil; Pinter, Stefan F.; Filion, Guillaume; Payer, Bernhard

doi:http://dx.doi.org/10.1038/s41467-021-23610-1

Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation

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Bauer M, Vidal E, Zorita E, Üresin N, Pinter SF, Filion GJ, Payer B. Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation. Nat Commun. 2021;12(1):3499. DOI: 10.1038/s41467-021-23610-1

Abstract

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.