Chromosome compartments on the inactive X guide TAD formation independently of transcription during X-reactivation
Bauer, M.; Vidal, E.; Zorita, E.; Üresin, N.; Pinter, S.F.; Filion, G.J.; Payer, B.
Nature Communications 12(1): 3499
2021
ISSN/ISBN: 2041-1723 PMID: 34108480 DOI: 10.1038/s41467-021-23610-1
Accession: 071435092
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.