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Review
. 2015 Oct 7;589(20 Pt A):2975-86.
doi: 10.1016/j.febslet.2015.06.008. Epub 2015 Jun 19.

Chromosome domain architecture and dynamic organization of the fission yeast genome

Takeshi Mizuguchi  1 , Jemima Barrowman  2 , Shiv I S Grewal  2
Affiliations
Review

Chromosome domain architecture and dynamic organization of the fission yeast genome

Takeshi Mizuguchi et al. FEBS Lett. .

Abstract

Advanced techniques including the chromosome conformation capture (3C) methodology and its derivatives are complementing microscopy approaches to study genome organization, and are revealing new details of three-dimensional (3D) genome architecture at increasing resolution. The fission yeast Schizosaccharomyces pombe (S. pombe) comprises a small genome featuring organizational elements of more complex eukaryotic systems, including conserved heterochromatin assembly machinery. Here we review key insights into genome organization revealed in this model system through a variety of techniques. We discuss the predominant role of Rabl-like configuration for interphase chromosome organization and the dynamic changes that occur during mitosis and meiosis. High resolution Hi-C studies have also revealed the presence of locally crumpled chromatin regions called "globules" along chromosome arms, and implicated a critical role for pericentromeric heterochromatin in imposing fundamental constraints on the genome to maintain chromosome territoriality and stability. These findings have shed new light on the connections between genome organization and function. It is likely that insights gained from the S. pombe system will also broadly apply to higher eukaryotes.

Keywords: Cohesin; Fission yeast; Genome organization; Heterochromatin; Hi-C; Rabl.

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Figures

Figure 1
Figure 1
Constitutive heterochromatin domains and the 3D organization of the S. pombe genome. (A) The three S. pombe chromosomes contain large blocks of heterochromatin that coats centromeres, telomeres and the silent mating-type (mat) interval. At centromeres, outer (otr) and innermost (imr) repeats surround the central core (cnt) domain, which is the site of kinetochore formation. The otr regions contain dg and dh repeats that are targets of heterochromatin formation by RNAi. tRNAs or IRC inverted repeats serve as heterochromatin boundary elements. A broad distribution of heterochromatin is also observed at the subtelomeric regions containing tlh1 and its paralogs, which contain a dh-like element within the coding region. The heterochromatin domain at the mat region contains silent mat2 and mat3 loci, which serve as donors of genetic information for the active mat1 locus. The cenH element with homology to dg and dh repeats nucleates heterochromatin, which in turn spreads across the domain surrounded by IR-L and IR-R inverted repeat boundary elements. Heterochromatin domains are highlighted in gray. (B). During interphase, chromosomes are arranged in a Rabl configuration. Interphase chromatin is subjected to various constraints and is confined to a limited sub-nuclear space (a degree of chromosome territory). (C) Tf2 retrotransposons dispersed across the genome are organized into discrete nuclear foci, called Tf bodies. CENP-B proteins collaborate with histone modifying activities such as HDACs and Set1 to form 2–3 Tf bodies in the nucleus.
Figure 2
Figure 2
General principles of S. pombe 3D genome organization as revealed by Hi-C. (A) The all-by-all contact map reveals that all three centromeres and telomeres of chromosome I and II form clusters. Centromeres avoid interactions with chromosomal arms. The specific inter-chromosomal interaction between the mat locus and tel1R suggests chromosome looping. Greater inter-arm contact compared to inter-chromosomal contact suggests chromosomal territoriality in the interphase nucleus. (B and C) Centromere-proximal inter-arm interactions and globules represent two key elements of S. pombe genome organization. The compaction of large heterochromatic domains around clustered centromeres promotes centromere-proximal intra- and inter-chromosomal inter-arm interactions and produces a cross-like interaction pattern. On chromosome arms, chromatin is organized into locally crumpled 50–100 kb repeating regions, referred to as “globules”. Globules are self-interacting domains that are observed along the diagonal of the Hi-C heatmap in both G1 and G2 cells.
Figure 3
Figure 3
Dynamic organization of interphase chromatin. Condensin regulates the spatial proximity of dispersed genetic elements such as tRNAs, 5S rRNAs and LTRs to the centromere. Condensin is recruited through distinct protein complexes. Condensin-mediated associations may facilitate chromosomal movements driven by microtubule dependent oscillation of the SPB. A molecular bridge formed by Csil and presumably other factors transmits the directional movement of the SPB to centromeres and condensin associated loci (large arrow).
Figure 4
Figure 4
Dynamic reconfiguration of chromosomes occurs during mitosis and meiosis. (A) The Rabl-like configuration in the interphase nucleus is transiently perturbed during mitosis. Centromeres dissociate from the SPB, while telomeres are de-clustered and released from the NE, liberating chromosomes for mitotic separation. Centromeres are recaptured by spindle microtubules, which are nucleated by the SPB buried in the NE, for proper chromosome segregation. Upon meiotic induction, the chromosomes reconfigure to form a polarized chromosomal array called the bouquet. This process is driven by dynamic cytoskeleton associated activities involving the SPB, telocentrosomes and motor proteins. The bouquet arrangement is achieved in two steps: (1) telomere movement to achieve bouquet clustering at the SPB and (2) centromere dissociation from the SPB. The functional 3D microenvironment created by these processes is critical for proper meiotic function (see text). Bundled telomeres at the SPB lead the nuclear oscillatory movements between the cell poles (horsetail shaped nucleus) for homologous pairing. After movement stops, chromosomes condense and cells initiate meiotic nuclear division. (B) Centromeres and telomeres are tethered to the NE through specific protein-protein interactions. The formation of the bouquet chromosome configuration is accomplished through changes in the molecular connections between chromatin associating proteins and nuclear membrane proteins, and is guided by dynamic cytoskeleton rearrangements.
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