2. Academic Validation
  3. Genome folding principles uncovered in condensin-depleted mitotic chromosomes

Genome folding principles uncovered in condensin-depleted mitotic chromosomes

  • Nat Genet. 2024 Jun;56(6):1213-1224. doi: 10.1038/s41588-024-01759-x.
Han Zhao 1,  Yinzhi Lin 1,  En Lin 1,  Fuhai Liu 1,  Lirong Shu 1,  Dannan Jing 1 2,  Baiyue Wang 1,  Manzhu Wang 1 3,  Fengnian Shan 1 4,  Lin Zhang 5,  Jessica C Lam 6 7,  Susannah C Midla 6,  Belinda M Giardine 8,  Cheryl A Keller 8,  Ross C Hardison 8,  Gerd A Blobel 9 10,  Haoyue Zhang 11
Affiliations

Affiliations

  • 1 Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China.
  • 2 Department of Biology, College of Science, Shantou University, Shantou, China.
  • 3 School of Basic Medicine, Capital Medical University, Beijing, China.
  • 4 School of Pharmacology, South China University of Technology, Guangzhou, China.
  • 5 School of Biological Science, Hongkong University, Hongkong, China.
  • 6 Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • 7 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 8 Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA.
  • 9 Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. blobel@chop.edu.
  • 10 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. blobel@chop.edu.
  • 11 Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China. zhang_adam@szbl.ac.cn.
PMID: 38802567 DOI: 10.1038/s41588-024-01759-x
Abstract

During mitosis, condensin activity is thought to interfere with interphase chromatin structures. To investigate genome folding principles in the absence of chromatin loop extrusion, we codepleted condensin I and condensin II, which triggered mitotic chromosome compartmentalization in ways similar to that in interphase. However, two distinct euchromatic compartments, indistinguishable in interphase, emerged upon condensin loss with different interaction preferences and dependencies on H3K27ac. Constitutive heterochromatin gradually self-aggregated and cocompartmentalized with facultative heterochromatin, contrasting with their separation during interphase. Notably, some cis-regulatory element contacts became apparent even in the absence of CTCF/cohesin-mediated structures. Heterochromatin protein 1 (HP1) proteins, which are thought to partition constitutive heterochromatin, were absent from mitotic chromosomes, suggesting, surprisingly, that constitutive heterochromatin can self-aggregate without HP1. Indeed, in cells traversing from M to G1 phase in the combined absence of HP1α, HP1β and HP1γ, constitutive heterochromatin compartments are normally re-established. In sum, condensin-deficient mitotic chromosomes illuminate forces of genome compartmentalization not identified in interphase cells.

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