A polymer model for large-scale chromatin organization in lower eukaryotes

Abstract

A quantitative model of large-scale chromatin organization was applied to nuclei of fission yeast Schizosaccharomyces pombe (meiotic prophase and G2 phase), budding yeast Saccharomyces cerevisiae (young and senescent cells), Drosophila (embryonic cycles 10 and 14, and polytene tissues) and Caenorhabditis elegans (G1 phase). The model is based on the coil-like behavior of chromosomal fibers and the tight packing of discrete chromatin domains in a nucleus. Intrachromosomal domains are formed by chromatin anchoring to nuclear structures (e.g., the nuclear envelope). The observed sizes for confinement of chromatin diffusional motion are similar to the estimated sizes of corresponding domains. The model correctly predicts chromosome configurations (linear, Rabl, loop) and chromosome associations (homologous pairing, centromere and telomere clusters) on the basis of the geometrical constraints imposed by nuclear size and shape. Agreement between the model predictions and literature observations supports the notion that the average linear density of the 30-nm chromatin fiber is approximately 4 nucleosomes per 10 nm contour length.

Figure 1

Schematic drawing of chromosome configurations in a nucleus. The configurations differ in their pattern of chromatin attachments to the nuclear structures: the nuclear envelope, nucleolus (crossed-hatched areas), etc. The chromosomal fiber can be anchored by telomeres (filled circles), centromeres (squares), and other sites (empty circles). The dashed lines represent discrete chromatin domains with length H_d and width Q_d. The chromosome length and width are H and Q, respectively. (A) Configuration I: linear, unattached chromosomes; (B) configuration II: linear, anchored by both telomeres; (C) configuration III: the Rabl orientation: folded, anchored by the centromere and both telomeres; (D) configuration IV: loop formed by an adjacent anchoring of both telomeres. The nuclei are ellipsoid (A–C) and pear-shaped (D).