Advancing our understanding of functional genome organisation through studies in the fission yeast

Abstract

Significant progress has been made in understanding the functional organisation of the cell nucleus. Still many questions remain to be answered about the relationship between the spatial organisation of the nucleus and the regulation of the genome function. There are many conflicting data in the field making it very difficult to merge published results on mammalian cells into one model on subnuclear chromatin organisation. The fission yeast, Schizosaccharomyces pombe, over the last decades has emerged as a valuable model organism in understanding basic biological mechanisms, especially the cell cycle and chromosome biology. In this review we describe and compare the nuclear organisation in mammalian and fission yeast cells. We believe that fission yeast is a good tool to resolve at least some of the contradictions and unanswered questions concerning functional nuclear architecture, since S. pombe has chromosomes structurally similar to that of human. S. pombe also has the advantage over higher eukaryotes in that the genome can easily be manipulated via homologous recombination making it possible to integrate the tools needed for visualisation of chromosomes using live-cell microscopy. Classical genetic experiments can be used to elucidate what factors are involved in a certain mechanism. The knowledge we have gained during the last few years indicates similarities between the genome organisation in fission yeast and mammalian cells. We therefore propose the use of fission yeast for further advancement of our understanding of functional nuclear organisation.

Fig. 1

The mating-type region in fission yeast contains a region with heterochromatin. The nucleation of heterochromatin formation occurs at cenH (dotted box) a region with 96% identity to the centromeric dg and dh repeats (Grewal and Klar 1997). Transcription of the repeats (curved lines) recruits HMT Clr4 that methylates histone H3 on lysine 9 (Me). This in turn creates a binding site for HP1 proteins, mostly Swi6, but also Chp1 and Chp2. The heterochromatin spreads until it reaches a boundary element, IR-L (black arrow), centromere-proximal or IR-R (black arrow) centromere-distal of the mating-type region

Fig. 2

The organisation of the fission yeast nucleus. The spindle pole body (SPB) is inserted into the nuclear membrane and the centromeres (CEN) and the mating-type region (MAT) are found together at the SPB. The telomeres (TEL) cluster in 2–3 foci at the opposite end of the nucleus where the nucleolus with the ribosomal DNA (rDNA) is found. The telomeres are attached to the NM via the action of Clr3, Bqt3 and Bqt4 proteins. A cluster of nitrogen-repressed genes (Chr1) is found at the nuclear periphery together with the telomeres in a Clr3-dependent manner

Fig. 3

The human cell nucleus according to different models. a The inter chromosome domain (ICD) model. The chromosomes are organised in distinct chromosome territories (grey) with higher order chromatin structures (black structures). Transcription by RNA polII (black dots) occurs in the interchromatin space. b The chromosome territory-interchromatin compartment (CT-IC) model. Also here the chromosomes are restricted to chromosome territories (grey) with higher order chromatin structures (black structures) with transcription by RNA polII (black dots) in the interchromatin space as well as in channels within the chromosome territories. c The lattice model with a mesh of chromatin fibres of 10 or 30 nm with extensive overlap between the chromosome territories (grey) and no distinct interchromosomal space. RNA polII (black dots) can freely diffuse in the chromatin mesh. d The ICN model where functional interaction between chromosomes (grey), probably by transcription factories (white oval marked TF), and attachment to fixed structures in the nucleus such as the nucleolus and the nuclear envelope forms the nuclear organisation