Genome maintenance in the context of 4D chromatin condensation

Abstract

The eukaryotic genome is packaged in the three-dimensional nuclear space by forming loops, domains, and compartments in a hierarchical manner. However, when duplicated genomes prepare for segregation, mitotic cells eliminate topologically associating domains and abandon the compartmentalized structure. Alongside chromatin architecture reorganization during the transition from interphase to mitosis, cells halt most DNA-templated processes such as transcription and repair. The intrinsically condensed chromatin serves as a sophisticated signaling module subjected to selective relaxation for programmed genomic activities. To understand the elaborate genome-epigenome interplay during cell cycle progression, the steady three-dimensional genome requires a time scale to form a dynamic four-dimensional and a more comprehensive portrait. In this review, we will dissect the functions of critical chromatin architectural components in constructing and maintaining an orderly packaged chromatin environment. We will also highlight the importance of the spatially and temporally conscious orchestration of chromatin remodeling to ensure high-fidelity genetic transmission.

Keywords: Cancer; Cell cycle; Chromatin architecture; Epigenome; Genome stability.

Fig. 1

Architecture of chromosome scaffold proteins. a–c SMC complexes including condensin I, II, and cohesion. The core of each SMC complex is formed by two SMC proteins; each SMC protein contains an ATPase head domain, a hinge domain and a coiled coil that links the two. In addition to SMC proteins, each condensin complex contains a kleisin protein (H stands for GAP-H in condensin I whereas H2 stands for CAP-H2 in condensin II) and two HEAT-repeat proteins (CAP-D2 and CAP-G in condensin I whereas CAP-D3 and CAP-G2 in condensin II). Cohesin is composed of SMC1 and SMC3 heterodimer, as well as a kleisin subunit (Rad21 or Scc1) that binds to HEAT-repeat subunits called SA1/SA2 or Scc3. d, e Type II topoisomerases use ATPase activity to cleave both strands of a duplex DNA (blue) and pass another duplex DNA (red) through the transient break

Fig. 2

Distinct chromatin organizations in interphase and mitotic cells and the two-step compaction process during the transition from interphase to mitosis. A hierarchical organization of chromatin loops, topologically associating domains and higher-order compartments is shown in the interphase cell (lower left corner). When the cell prepares for division, linear compaction results in the formation of 80–120 kb consecutive loops. Further axial and lateral compression ultimately gives rise to the rod-shaped mitotic chromosome. CTCF (red barrel) and cohesion (green ring) cooperate to form and stabilize chromatin domains. Two models of cohesion anchoring chromatin loops are shown in the box. In the mitotic cell, the different colored rings (match Fig. 1) represent condensin I (blue), condensin II (brown), and cohesin (green)