Poly(dA:dT) tracts: major determinants of nucleosome organization
Section snippets
Functional importance of poly(dA:dT) tracts in vivo
Poly(dA:dT) tracts — homopolymeric stretches of deoxyadenosine nucleotides (A's), often having lengths of 10–20 bp or even greater — are highly enriched in eukaryotic genomes but, intriguingly, not in prokaryotic genomes [1], suggesting that they may have a functional role unique to eukaryotic genomes. Indeed, studies of many individual genes showed that poly(dA:dT) tracts are important for transcriptional regulation [2••, 3••, 4, 5, 6], recombination [7], and blocking the spread of histone
Poly(dA:dT) tracts and their flanking DNA are relatively depleted of nucleosomes in vivo
The possibility that poly(dA:dT) tracts might function in vivo to facilitate gene activation by excluding nucleosomes [2••] focused attention on the nucleosome organization around poly(dA:dT) tracts at many genes [2••, 3••, 4, 5, 6, 7, 12, 13, 14, 15, 16]. The results of these studies at individual loci were conflicting, in part because some were not carried out quantitatively. Certain assays for nucleosome occupancy can sensitively reveal the presence of nucleosome-free DNA even if a given
Nucleosome depletion over poly(dA:dT) tracts results chiefly from the tracts’ intrinsically lower nucleosome affinity
What causes the dramatic nucleosome depletion over poly(dA:dT) tracts? The simplest hypothesis, that the nucleosome depletion is due to competition with another protein that binds specifically to poly(dA:dT) tracts, is ruled out. To date, a single protein in Saccharomyces cerevisiae, called Datin (Dat1p), which recognizes poly(dA:dT) tracts of length 9 bp or greater, has been identified [23]. Datin may be the only DNA binding protein in S. cerevisiae that binds poly(dA:dT) tracts, since yeast
Poly(dA:dT) tracts have unusual structural and dynamic properties
At the level of detailed molecular structure and mechanics, why is it that nucleosomes intrinsically disfavor wrapping poly(dA:dT) tracts relative to most other DNA sequences? The answer is not known definitively; but a growing body of studies points to a unique cooperative structure of poly(dA:dT) tracts, which in turn is associated with, and possibly owing to, a unique hydration structure of the poly(dA:dT) tracts. Deforming this unique poly(dA:dT) tract structure by forcing it into a
Conclusions
In summary, poly(dA:dT) tracts strongly resist incorporation into nucleosomes in vitro, and, if incorporated into nucleosomes, reduce the stability of those nucleosomes. This intrinsic resistance to incorporation into nucleosomes may be because of an intrinsic resistance of the poly(dA:dT) tracts to adopting the substantially distorted structures required by the nucleosome, although this idea remains unproven. Whatever the physical mechanism for their preferential avoidance of nucleosome
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
•• of outstanding interest
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