Poly(dA:dT) tracts: major determinants of nucleosome organization - PubMed (original) (raw)

Review

Poly(dA:dT) tracts: major determinants of nucleosome organization

Eran Segal et al. Curr Opin Struct Biol. 2009 Feb.

Abstract

Homopolymeric stretches of deoxyadenosine nucleotides (A's) on one strand of double-stranded DNA, referred to as poly(dA:dT) tracts or A-tracts, are overabundant in eukaryotic genomes. They have unusual structural, dynamic, and mechanical properties, and may resist sharp bending. Such unusual material properties, together with their overabundance in eukaryotes, raised the possibility that poly(dA:dT) tracts might function in eukaryotes to influence the organization of nucleosomes at many genomic regions. Recent genome-wide studies strongly confirm these ideas and suggest that these tracts play major roles in chromatin organization and genome function. Here we review what is known about poly(dA:dT) tracts and how they work.

PubMed Disclaimer

Figures

Figure 1

Figure 1. Nucleosome are relatively depleted over poly(dA:dT) tracts in vivo

Shown is the combined nucleosome fold depletion over all poly(dA:dT) tracts of length k, for k = 5,6,7,…, and for tracts with exactly 0, 2, 4, or 6 base substitutions. Each graph is trimmed at a length K at which there are less than 10 such tracts in the S. cerevisiae genome, and the fold depletion at this final point is computed over all elements whose length is at least K. The number of underlying elements at various points in the graph is indicated (N). Figure adapted from ref. [**9].

Figure 2

Figure 2. Poly(dA:dT) tracts create larger nucleosome-depleted regions

(a) Shown is a simple example focusing only on the immediate neighborhood of the boundary. All (five) possible nucleosome configurations are illustrated, in which a nucleosome (cyan ovals) can be placed within five basepairs of the boundary (blue triangle). The number and set of nucleosome configurations occupying each of the five basepairs immediately adjacent to the boundary are shown in the graph below. If all configurations are equally likely, then basepairs closer to the poly(dA:dT) tract will exhibit lower nucleosome occupancy simply because fewer nucleosome configurations cover those basepairs [22]. (b) Schematic showing that nucleosome depletion caused by a poly(dA:dT) tract is maximal over the tract itself, but extends for considerable distances in either direction. Thus specific factor DNA binding sites located nearby to a poly(dA:dT) tract will have relatively enhanced accessibility compared to factor sites located far from a poly(dA:dT) tract, facilitating binding of the factor. Panel (a) adapted from ref. [**9].

Figure 3

Figure 3. Narrow minor groove and multilayer spine of hydration in a poly(dA:dT) tract

Shown is a representation of the atomic resolution X-ray crystallographic structure of [d(CGCAAATTTGCG)]2 [**44]. The DNA backbones are shown as yellow curves, with the bases shown in a partial-charge-coded stick representation. The narrow minor groove of the A3T3 stretch has many high occupancy water molecules, 4 layers deep, shown here as spheres, color coded according to their layer from innermost to outermost as cyan, purple, blue, and red, respectively. The multiple layers, extensive hydrogen bonding, and high occupancy of these waters all suggest that they may have strongly favorable energetic interactions with themselves and the DNA. Figure kindly provided by Prof. L.D. Williams (Georgia Tech.).

Similar articles

Cited by

References

    1. Dechering KJ, Cuelenaere K, Konings RN, Leunissen JA. Distinct frequency-distributions of homopolymeric DNA tracts in different genomes. Nucleic Acids Research. 1998;26:4056–4062. - PMC - PubMed
    1. Struhl K. Naturally occurring poly(dA-dT) sequences are upstream promoter elements for constitutive transcription in yeast. Proc Natl Acad Sci USA. 1985;82:8419–8423. This paper was the first to report that poly(dA:dT) elements in a gene’s promoter facilitate transcription in vivo, and the first to connect this observation with a possible mechanism, suggesting that poly(dA:dT) elements could act by depleting repressive nucleosomes from the promoter. - PMC - PubMed
    1. Iyer V, Struhl K. Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure. EMBO J. 1995;14:2570–2579. This paper was the first to provide concrete evidence in support of the model in which poly(dA:dT) elements act by depleting repressive nucleosomes from a gene’s promoter, thereby effectively enhancing transcription. - PMC - PubMed
    1. Moreira JM, Remacle JE, Kielland-Brandt MC, Holmberg S. Datin, a yeast poly(dA:dT)-binding protein, behaves as an activator of the wild-type ILV1 promoter and interacts synergistically with Reb1p. Mol Gen Genet. 1998;258:95–103. - PubMed
    1. Lascaris RF, Groot E, Hoen PB, Mager WH, Planta RJ. Different roles for abf1p and a T-rich promoter element in nucleosome organization of the yeast RPS28A gene. Nucleic Acids Research. 2000;28:1390–1396. - PMC - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources