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Distinct modes of regulation by chromatin encoded through nucleosome positioning signals.

Field Y, Kaplan N, Fondufe-Mittendorf Y, Moore IK, Sharon E, Lubling Y, Widom J, Segal E - PLoS Comput. Biol. (2008)

Bottom Line: The detailed positions of nucleosomes profoundly impact gene regulation and are partly encoded by the genomic DNA sequence.We find that Poly(dA:dT) tracts are an important component of these nucleosome positioning signals and that their nucleosome-disfavoring action results in large nucleosome depletion over them and over their flanking regions and enhances the accessibility of transcription factors to their cognate sites.Our results suggest that the yeast genome may utilize these nucleosome positioning signals to regulate gene expression with different transcriptional noise and activation kinetics and DNA replication with different origin efficiency.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.

ABSTRACT
The detailed positions of nucleosomes profoundly impact gene regulation and are partly encoded by the genomic DNA sequence. However, less is known about the functional consequences of this encoding. Here, we address this question using a genome-wide map of approximately 380,000 yeast nucleosomes that we sequenced in their entirety. Utilizing the high resolution of our map, we refine our understanding of how nucleosome organizations are encoded by the DNA sequence and demonstrate that the genomic sequence is highly predictive of the in vivo nucleosome organization, even across new nucleosome-bound sequences that we isolated from fly and human. We find that Poly(dA:dT) tracts are an important component of these nucleosome positioning signals and that their nucleosome-disfavoring action results in large nucleosome depletion over them and over their flanking regions and enhances the accessibility of transcription factors to their cognate sites. Our results suggest that the yeast genome may utilize these nucleosome positioning signals to regulate gene expression with different transcriptional noise and activation kinetics and DNA replication with different origin efficiency. These distinct functions may be achieved by encoding both relatively closed (nucleosome-covered) chromatin organizations over some factor binding sites, where factors must compete with nucleosomes for DNA access, and relatively open (nucleosome-depleted) organizations over other factor sites, where factors bind without competition.

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Nucleosome depleted regions are created in the vicinity of Poly(dA:dT) boundaries.(A) A boundary constraint creates, on average, a larger nucleosome-depleted region that extends far into regions flanking the boundary. 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 and table, respectively. If all configurations are equally likely, then basepairs closer to the boundary will exhibit lower nucleosome occupancy. (B) Boundaries exhibit strong and long-range nucleosome depletion regardless of whether they are near transcription factor binding sites or whether they are in promoters or non-promoter intergenic regions. Shown is the average number of nucleosome reads in our data at locations k (for k = 1,2,…,150) basepairs away from boundaries (strength >5) that are: more than 30 bp from any factor site (green); within 30 bp of a factor site bound by its cognate factor [47] (purple); in intergenic regions that are not promoters (orange). The strength of a boundary is defined by properties of the DNA sequence of the boundary, based on the length and perfection of the Poly(dA:dT) components of the boundary (see Methods). Plots are symmetric by construction. (C) Boundaries enhance the accessibility of transcription factors to cognate sites. Shown is the average number of nucleosome reads in our data at locations k (for k = 1,2,…,150) basepairs away from annotated factor binding sites bound by their cognate factor [47] that are: more than 30 bp from any boundary (boundary strength >5) (blue); within 30 bp of any boundary (strength >5) (red). Plots are symmetric by construction.
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pcbi-1000216-g007: Nucleosome depleted regions are created in the vicinity of Poly(dA:dT) boundaries.(A) A boundary constraint creates, on average, a larger nucleosome-depleted region that extends far into regions flanking the boundary. 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 and table, respectively. If all configurations are equally likely, then basepairs closer to the boundary will exhibit lower nucleosome occupancy. (B) Boundaries exhibit strong and long-range nucleosome depletion regardless of whether they are near transcription factor binding sites or whether they are in promoters or non-promoter intergenic regions. Shown is the average number of nucleosome reads in our data at locations k (for k = 1,2,…,150) basepairs away from boundaries (strength >5) that are: more than 30 bp from any factor site (green); within 30 bp of a factor site bound by its cognate factor [47] (purple); in intergenic regions that are not promoters (orange). The strength of a boundary is defined by properties of the DNA sequence of the boundary, based on the length and perfection of the Poly(dA:dT) components of the boundary (see Methods). Plots are symmetric by construction. (C) Boundaries enhance the accessibility of transcription factors to cognate sites. Shown is the average number of nucleosome reads in our data at locations k (for k = 1,2,…,150) basepairs away from annotated factor binding sites bound by their cognate factor [47] that are: more than 30 bp from any boundary (boundary strength >5) (blue); within 30 bp of any boundary (strength >5) (red). Plots are symmetric by construction.

Mentions: Another possibility is that the binding of transcription factors to sites near the boundaries causes nucleosome depletion over boundaries. Indeed, such an effect is to be expected on thermodynamic grounds; the question is the relative significance of this effect. To test this, we compared the nucleosome occupancy over boundaries that are near factor binding sites, to that over boundaries that are far from factor sites. We find strong nucleosome depletion over boundaries regardless of whether or not they are near factor sites (Figure 7B). This result is not sensitive to binding site annotations, since we find a similar strong depletion over boundaries in intergenic regions that are not promoters, thought to be largely devoid of factor sites (Figure 7B). These results suggest that transcription factor binding is not the main cause of nucleosome depletion over the boundary sequences.


Distinct modes of regulation by chromatin encoded through nucleosome positioning signals.

Field Y, Kaplan N, Fondufe-Mittendorf Y, Moore IK, Sharon E, Lubling Y, Widom J, Segal E - PLoS Comput. Biol. (2008)

Nucleosome depleted regions are created in the vicinity of Poly(dA:dT) boundaries.(A) A boundary constraint creates, on average, a larger nucleosome-depleted region that extends far into regions flanking the boundary. 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 and table, respectively. If all configurations are equally likely, then basepairs closer to the boundary will exhibit lower nucleosome occupancy. (B) Boundaries exhibit strong and long-range nucleosome depletion regardless of whether they are near transcription factor binding sites or whether they are in promoters or non-promoter intergenic regions. Shown is the average number of nucleosome reads in our data at locations k (for k = 1,2,…,150) basepairs away from boundaries (strength >5) that are: more than 30 bp from any factor site (green); within 30 bp of a factor site bound by its cognate factor [47] (purple); in intergenic regions that are not promoters (orange). The strength of a boundary is defined by properties of the DNA sequence of the boundary, based on the length and perfection of the Poly(dA:dT) components of the boundary (see Methods). Plots are symmetric by construction. (C) Boundaries enhance the accessibility of transcription factors to cognate sites. Shown is the average number of nucleosome reads in our data at locations k (for k = 1,2,…,150) basepairs away from annotated factor binding sites bound by their cognate factor [47] that are: more than 30 bp from any boundary (boundary strength >5) (blue); within 30 bp of any boundary (strength >5) (red). Plots are symmetric by construction.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570626&req=5

pcbi-1000216-g007: Nucleosome depleted regions are created in the vicinity of Poly(dA:dT) boundaries.(A) A boundary constraint creates, on average, a larger nucleosome-depleted region that extends far into regions flanking the boundary. 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 and table, respectively. If all configurations are equally likely, then basepairs closer to the boundary will exhibit lower nucleosome occupancy. (B) Boundaries exhibit strong and long-range nucleosome depletion regardless of whether they are near transcription factor binding sites or whether they are in promoters or non-promoter intergenic regions. Shown is the average number of nucleosome reads in our data at locations k (for k = 1,2,…,150) basepairs away from boundaries (strength >5) that are: more than 30 bp from any factor site (green); within 30 bp of a factor site bound by its cognate factor [47] (purple); in intergenic regions that are not promoters (orange). The strength of a boundary is defined by properties of the DNA sequence of the boundary, based on the length and perfection of the Poly(dA:dT) components of the boundary (see Methods). Plots are symmetric by construction. (C) Boundaries enhance the accessibility of transcription factors to cognate sites. Shown is the average number of nucleosome reads in our data at locations k (for k = 1,2,…,150) basepairs away from annotated factor binding sites bound by their cognate factor [47] that are: more than 30 bp from any boundary (boundary strength >5) (blue); within 30 bp of any boundary (strength >5) (red). Plots are symmetric by construction.
Mentions: Another possibility is that the binding of transcription factors to sites near the boundaries causes nucleosome depletion over boundaries. Indeed, such an effect is to be expected on thermodynamic grounds; the question is the relative significance of this effect. To test this, we compared the nucleosome occupancy over boundaries that are near factor binding sites, to that over boundaries that are far from factor sites. We find strong nucleosome depletion over boundaries regardless of whether or not they are near factor sites (Figure 7B). This result is not sensitive to binding site annotations, since we find a similar strong depletion over boundaries in intergenic regions that are not promoters, thought to be largely devoid of factor sites (Figure 7B). These results suggest that transcription factor binding is not the main cause of nucleosome depletion over the boundary sequences.

Bottom Line: The detailed positions of nucleosomes profoundly impact gene regulation and are partly encoded by the genomic DNA sequence.We find that Poly(dA:dT) tracts are an important component of these nucleosome positioning signals and that their nucleosome-disfavoring action results in large nucleosome depletion over them and over their flanking regions and enhances the accessibility of transcription factors to their cognate sites.Our results suggest that the yeast genome may utilize these nucleosome positioning signals to regulate gene expression with different transcriptional noise and activation kinetics and DNA replication with different origin efficiency.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.

ABSTRACT
The detailed positions of nucleosomes profoundly impact gene regulation and are partly encoded by the genomic DNA sequence. However, less is known about the functional consequences of this encoding. Here, we address this question using a genome-wide map of approximately 380,000 yeast nucleosomes that we sequenced in their entirety. Utilizing the high resolution of our map, we refine our understanding of how nucleosome organizations are encoded by the DNA sequence and demonstrate that the genomic sequence is highly predictive of the in vivo nucleosome organization, even across new nucleosome-bound sequences that we isolated from fly and human. We find that Poly(dA:dT) tracts are an important component of these nucleosome positioning signals and that their nucleosome-disfavoring action results in large nucleosome depletion over them and over their flanking regions and enhances the accessibility of transcription factors to their cognate sites. Our results suggest that the yeast genome may utilize these nucleosome positioning signals to regulate gene expression with different transcriptional noise and activation kinetics and DNA replication with different origin efficiency. These distinct functions may be achieved by encoding both relatively closed (nucleosome-covered) chromatin organizations over some factor binding sites, where factors must compete with nucleosomes for DNA access, and relatively open (nucleosome-depleted) organizations over other factor sites, where factors bind without competition.

Show MeSH