Re-configuration of Chromatin Structure During the Mitosis-G1 Phase Transition

Zhang, H.; Emerson, D.; Gilgenast, T.; Titus, K.; Lan, Y.; Huang, P.; Zhang, D.; Wang, H.; Keller, C.; Giardine, B.; Hardison, R.; Phillips-Cremins, J.; Blobel, G.

doi:10.1101/604355

bioRxiv · 10.1101/604355

Re-configuration of Chromatin Structure During the Mitosis-G1 Phase Transition

Zhang, H.·Emerson, D.·Gilgenast, T.·Titus, K.·Lan, Y.·Huang, P.·Zhang, D.·Wang, H.·Keller, C.·Giardine, B.·Hardison, R.·Phillips-Cremins, J.·Blobel, G.

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Abstract

Higher-order chromatin organization such as A/B compartments, TADs and chromatin loops are temporarily disrupted during mitosis. These structures are thought to organize aspects of gene regulation, and thus it is important to understand how they are re-established after mitosis. We examined the dynamics of chromosome reorganization by Hi-C at defined time points following exit from mitosis in highly purified, synchronous cell populations. We observed that A/B compartments are rapidly established and progressively gain in strength following mitotic exit. Contact domain formation occurs from the \"bottom-up\" with smaller sub-TADs forming initially, followed by convergence into multi-domain TAD structures. CTCF is strongly retained at a significant fraction of sites on mitotic chromosomes and immediately resumes full binding at ana/telophase, the earliest tested time point. In contrast, cohesin is completely evicted from mitotic chromosomes and resumes focal binding with delayed kinetics. The formation of CTCF/cohesin co-anchored structural loops follows the kinetics of cohesin positioning. Stripe-shaped contacts anchored by CTCF grow in length, consistent with a loop extrusion process after mitosis. Interactions between cis-regulatory elements can form rapidly, preceding CTCF/cohesin anchored structural loops. 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. Our findings indicate that distinct but mutually influential forces drive post-mitotic chromatin re-configuration to shape compartments, contact domains, cis-element contacts, and CTCF/cohesin dependent loops.

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Zhang, H., Emerson, D., Gilgenast, T., Titus, K., Lan, Y., Huang, P., Zhang, D., Wang, H., Keller, C., Giardine, B., Hardison, R., Phillips-Cremins, J., Blobel, G.. 2019-04-11. Re-configuration of Chromatin Structure During the Mitosis-G1 Phase Transition. https://doi.org/10.1101/604355

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