Chromosome conformation maps in fission yeast reveal cell cycle dependent sub nuclear structure.

Ralph S Grand,Lutz R Gehlen,Jane R Allison,Peter Tsai,M Beatrix Jones,Tatyana Pichugina,Justin M O'Sullivan,Robert Martienssen

doi:10.1093/nar/gku965

Abstract

Successful progression through the cell cycle requires spatial and temporal regulation of gene transcript levels and the number, positions and condensation levels of chromosomes. Here we present a high resolution survey of genome interactions in Schizosaccharomyces pombe using synchronized cells to investigate cell cycle dependent changes in genome organization and transcription. Cell cycle dependent interactions were captured between and within S. pombe chromosomes. Known features of genome organization (e.g. the clustering of telomeres and retrotransposon long terminal repeats (LTRs)) were observed throughout the cell cycle. There were clear correlations between transcript levels and chromosomal interactions between genes, consistent with a role for interactions in transcriptional regulation at specific stages of the cell cycle. In silico reconstructions of the chromosome organization within the S. pombe nuclei were made by polymer modeling. These models suggest that groups of genes with high and low, or differentially regulated transcript levels have preferred positions within the S. pombe nucleus. We conclude that the S. pombe nucleus is spatially divided into functional sub-nuclear domains that correlate with gene activity. The observation that chromosomal interactions are maintained even when chromosomes are fully condensed in M phase implicates genome organization in epigenetic inheritance and bookmarking.

Highlights

The spatial and temporal organization of the genome are increasingly recognized as key contributors to genome maintenance and gene regulation in both prokaryotes and eukaryotes [1,2,3,4,5]
In particular observations that: (i) eukaryotic chromosomes exist in territories [13]; (ii) topologically associated domains (TADs) form within chromosomes [12,14,15]; (iii) transcription and replication factories form within nuclei (e.g. [16]); and (iv) highly transcribed genes associate in space [8], are thought to be important for the translation of the genotype into the cell’s phenotype
Cell growth proceeds in an ordered manner through a regulated cycle consisting of the gap 1 (G1), synthesis (S), gap 2 (G2) and mitotic (M) phases

Summary

Introduction

The spatial and temporal organization of the genome are increasingly recognized as key contributors to genome maintenance and gene regulation in both prokaryotes and eukaryotes [1,2,3,4,5]. Naumova et al succeeded in interrogating the intrachromosomal organization, focusing on the mitotic phase structures, of particular chromosomes in human HeLaS3, K562 and primary human foreskin fibroblast cells [12]. They observed high levels of correlation between the intrachromosomal organization patterns for early G1, mid G1 and S phase chromosomes

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Conclusion