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

Haoyue Zhang, Daniel J. Emerson, Thomas G. Gilgenast, Katelyn R. Titus, Yemin Lan, Peng Huang, Di Zhang, Hongxin Wang, Cheryl A. Keller, Belinda Giardine, Ross C. Hardison, Jennifer E Phillips-Cremins, Gerd A. Blobel
doi: https://doi.org/10.1101/604355
Haoyue Zhang
1Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
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Daniel J. Emerson
2Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Thomas G. Gilgenast
2Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Katelyn R. Titus
2Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Yemin Lan
3Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
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Peng Huang
1Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
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Di Zhang
1Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
3Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
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Hongxin Wang
1Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
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Cheryl A. Keller
4Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
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Belinda Giardine
4Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
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Ross C. Hardison
4Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
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Jennifer E Phillips-Cremins
2Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA
3Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
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  • For correspondence: blobel@email.chop.edu jcremins@seas.upenn.edu
Gerd A. Blobel
1Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
3Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
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  • For correspondence: blobel@email.chop.edu jcremins@seas.upenn.edu
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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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Posted April 11, 2019.
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Re-configuration of Chromatin Structure During the Mitosis-G1 Phase Transition
Haoyue Zhang, Daniel J. Emerson, Thomas G. Gilgenast, Katelyn R. Titus, Yemin Lan, Peng Huang, Di Zhang, Hongxin Wang, Cheryl A. Keller, Belinda Giardine, Ross C. Hardison, Jennifer E Phillips-Cremins, Gerd A. Blobel
bioRxiv 604355; doi: https://doi.org/10.1101/604355
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Re-configuration of Chromatin Structure During the Mitosis-G1 Phase Transition
Haoyue Zhang, Daniel J. Emerson, Thomas G. Gilgenast, Katelyn R. Titus, Yemin Lan, Peng Huang, Di Zhang, Hongxin Wang, Cheryl A. Keller, Belinda Giardine, Ross C. Hardison, Jennifer E Phillips-Cremins, Gerd A. Blobel
bioRxiv 604355; doi: https://doi.org/10.1101/604355

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