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

Moritz Bauer, Enrique Vidal, Eduard Zorita, Nil Üresin, Stefan F. Pinter, Guillaume J. Filion () and Bernhard Payer ()
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Moritz Bauer: The Barcelona Institute of Science and Technology
Enrique Vidal: The Barcelona Institute of Science and Technology
Eduard Zorita: The Barcelona Institute of Science and Technology
Nil Üresin: The Barcelona Institute of Science and Technology
Stefan F. Pinter: Institute for Systems Genomics, University of Connecticut Health Center
Guillaume J. Filion: The Barcelona Institute of Science and Technology
Bernhard Payer: The Barcelona Institute of Science and Technology

Nature Communications, 2021, vol. 12, issue 1, 1-21

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-23610-1

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