SMC complexes orchestrate the mitotic chromatin interaction landscape

Abstract

Chromatin is a very long DNA-protein complex that controls the expression and inheritance of the genetic information. Chromatin is stored within the nucleus in interphase and further compacted into chromosomes during mitosis. This process, known as chromosome condensation, is essential for faithful segregation of genomic DNA into daughter cells. Condensin and cohesin, members of the structural maintenance of chromosomes (SMC) family, are fundamental for chromosome architecture, both for establishment of chromatin structure in the interphase nucleus and for the formation of condensed chromosomes in mitosis. These ring-shaped SMC complexes are thought to regulate the interactions between DNA strands by topologically entrapping DNA. How this activity shapes chromosomes is not yet understood. Recent high throughput chromosome conformation capture studies revealed how chromatin is reorganized during the cell cycle and have started to explore the role of SMC complexes in mitotic chromatin architecture. Here, we summarize these findings and discuss the conserved nature of chromosome condensation in eukaryotes. We highlight the unexpected finding that condensin-dependent intra-chromosomal interactions in mitosis increase within a distinctive distance range that is characteristic for an organism, while longer and shorter-range interactions are suppressed. This reveals important molecular insight into chromosome architecture.

Keywords: Cell cycle; Chromatin; Chromosome condensation; Hi-C; SMC complex.

Fig. 1

Contact probabilities as a function of genomic distance in three organisms. a–c Contact probabilities in interphase (blue) and in mitosis (red) are shown as a function of genomic distance in fission yeast (a), budding yeast (b) and human cells (c). The gray squares highlight the area enriched for chromatin interactions in mitosis. Arrows indicate changes of contact probabilities between interphase and mitosis

Fig. 2

Schematic of condensin-mediated chromosome condensation. Many small domains are formed in interphase. Condensin replaces local contacts with longer-range interactions, resulting in the formation of larger domains. In parallel, condensin confines chromatin motility. Domains are shown as gray circles. One-dimensional position of chromatin is shown as color gradient