Chromatin structure dynamics during the mitosis-to-G1 phase transition.

Abstract

SUMMARY:Higher-order chromatin organization such as A/B compartments, TADs, and chromatin loops are temporarily disrupted during mitosis1,2. Since these structures are thought to influence gene regulation, it is important to understand how they are re-established after mitosis. We examined the dynamics of chromosome reorganization by Hi-C after mitosis in highly purified, synchronous cell populations. We observed rapid establishment, gradual intensification, and expansion of A/B compartments. Contact domains form from the “bottom-up” with smaller subTADs forming initially, followed by convergence into multi-domain TAD structures. CTCF is partially retained on mitotic chromosomes and immediately resumes full binding at ana/telophase. In contrast, cohesin is completely evicted from mitotic chromosomes and regains focal binding with delayed kinetics. The formation of CTCF/cohesin co-anchored structural loops follows the kinetics of cohesin positioning. Stripe-shaped contact patterns anchored by CTCF grow in length, consistent with a loop extrusion process after mitosis. Interactions between cis-regulatory elements can form rapidly with their rates exceeding those of CTCF/cohesin anchored contacts. Strikingly, we identified a group of rapidly emerging transient contacts between cis-regulatory elements in ana/telophase, that are dissolved upon G1 entry, co-incident with the establishment of inner boundaries or nearby interfering loops. We also describe the relationship between transcription reactivation and architectural features. Our findings indicate that distinct but mutually influential forces drive post-mitotic chromatin re-configuration.