The DNA sequence-dependence of nucleosome positioning in vivo and in vitro

Abstract

The contribution of histone-DNA interactions to nucleosome positioning in vivo is currently a matter of debate. We argue here that certain nucleosome positions, often in promoter regions, in yeast may be, at least in part, specified by the DNA sequence. In contrast other positions may be poorly specified. Positioning thus has both statistical and DNA-determined components. We further argue that the relative affinity of the octamer for different DNA sequences can vary and therefore the interaction of histones with the DNA is a 'tunable' property.

Figure 1

DNA periodicity profiles. The periodicity index Is a measure of coherence of periodicity patterns of e.g., AA/TT and GC over a given length of DNA, usually empirically 50 bp. A helical periodicity of ~10 bp is assumed. If direction of bending changes, the phase of the periodic sequence patterns will change and will interfere with phase of adjacent sequences. A high value of the index indicates the sequence periodicities are strong and coherent over the window chosen. (A) Saccharomyces cerevisiae recombination enhancer (reproduced with permission from ref. 51). Blue arrows indicate centres of positions mapped by partial MNase digestion. Coordinates refer to the nucleotide positions in the appropriate chromosome. (B) 5′ LTR of HIV. In vivo (red ellipses) and in vitro (blue ellipse) nucleosome positions for HIV are taken from ref. . Nucleotide indicates the numbers of nucleotides from the 5′ end of the LTR. Lh panel: periodicity profile; rh panel: stacking energy superimposed on periodicity profile. Note that regions of high stacking energy (high negative ΔG) fall within or flank nuclease hypersensitive sites (HS).

Figure 2

Coupling of nucleosome positioning and chromatin compaction. An array with irregular nucleosome spacing can, in principle, fold to form a 30 nm fibre with a packing density of ~6 nucs/11 nm. When the nucleosomes are regularly spaced at ‘optimal’ distances (121) tight stacking of adjacent nucleosomes can occur. With irregular spacing tight stacking is precluded because the nucleosomes would be inclined at differing orientations to the superhelical axis. The 30 nm fibres are represented as 2-start structures with the two helical stacks of nucleosomes coloured in red and blue.