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Review
. 2013 Mar;20(3):267-73.
doi: 10.1038/nsmb.2506.

Determinants of nucleosome positioning

Kevin Struhl  1 , Eran Segal
Affiliations
Review

Determinants of nucleosome positioning

Kevin Struhl et al. Nat Struct Mol Biol. 2013 Mar.

Abstract

Nucleosome positioning is critical for gene expression and most DNA-related processes. Here we review the dominant patterns of nucleosome positioning that have been observed and summarize the current understanding of their underlying determinants. The genome-wide pattern of nucleosome positioning is determined by the combination of DNA sequence, ATP-dependent nucleosome remodeling enzymes and transcription factors that include activators, components of the preinitiation complex and elongating RNA polymerase II. These determinants influence each other such that the resulting nucleosome positioning patterns are likely to differ among genes and among cells in a population, with consequent effects on gene expression.

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Figures

Figure 1
Figure 1. Illustration of the concepts of nucleosome positioning and nucleosome occupancy
(A) Nucleosome positioning along every basepair in the genome is defined as the fraction of cells from the population in which that basepair is at the center of a 147bp nucleosome. Shown are illustrations of a 147bp region with perfect positioning (left), in which the nucleosome center is located at the same basepair across all cells; a 147bp region with partial positioning, in which there is a preference for some locations; and a 147bp region with no positioning, in which all locations have equal probability. (B) Nucleosome occupancy along every basepair in the genome is defined as the fraction of cells from the population in which the basepair is occupied by any histone octamer. Shown is an illustration of nucleosome locations across a cell population (top), and the resulting nucleosome occupancy per basepair (bottom).
Figure 2
Figure 2. Illustration of nucleosome sequence preferences
Within the 147bp that are wrapped around the histone octamer, there is a preference for distinctive di-nucleotides that recur periodically at the DNA helical repeat and are known to facilitate the sharp bending of DNA around the nucleosome. These include ~10-bp periodic AA/TT/TA dinucleotides that oscillate in phase with each other and out of phase with ~10-bp periodic GC dinucleotides. The linker regions exhibit a strong preference for sequences that resist DNA bending and thus disfavor nucleosome formation. Among these poly(dA:dT) tracts and their variants are most dominant and highly enriched in eukaryotic promoters.
Figure 3
Figure 3
Determinants of nucleosome positioning. (a) Nucleosome-depleted regions (NDRs) are generated either by poly (dA:dT) tracts and/or by transcription factors and their recruited nucleosome remodeling complexes. Gray circles indicate nucleosomes. (b) Nucleosomes located at highly preferred positions (black circles) flanking the NDR are generated by nucleosome-remodeling complexes (for example, Isw2 and RSC, likely in a transcription-independent manner), and fine-tuned by the Pol II preinitiation complex (PIC) and associated factors. (c) Positioning of the more downstream nucleosomes depends on transcriptional elongation, and the recruitment of nucleosome-remodeling activities (for example, Chd1 and Isw1) and histone chaperones by the elongating Pol II machinery. This figure, which was modified from ref. , does not include DNA sequence determinants of rotational positioning (Fig. 2) or contributions to nucleosome spacing by histone H1.
See this image and copyright information in PMC

Comment in

  • The dynamic epigenome.
    [No authors listed] [No authors listed] Nat Struct Mol Biol. 2013 Mar;20(3):258. doi: 10.1038/nsmb.2534. Nat Struct Mol Biol. 2013. PMID: 23463309 No abstract available.

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