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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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Boundaries enhance the accessibility of transcription factors to their cognate binding sites.(A) Nucleosome depletion over factor sites increases with their proximity to, and with the strength of, boundaries. Shown is the combined nucleosome fold depletion over factor sites (y-axis) that are within a certain range of distances from boundaries that themselves have a particular nucleosome fold depletion (boundary strength; x-axis). Plots are shown for four different ranges of factor-boundary distances and for the four boundary strength groups of nucleosome fold depletions that we defined based on sequence rules (see Methods). (B) Factor binding sites near boundaries are depleted of nucleosomes. For each factor, shown is the combined nucleosome fold depletion over its annotated sites [47],[67] that are within 30 bp from a boundary whose fold depletion is at least 5 (blue bars), and over the rest of its sites (green bars). The combined fold depletion of a set of genomic elements is the ratio between their expected and observed nucleosome coverage (see Methods).
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pcbi-1000216-g010: Boundaries enhance the accessibility of transcription factors to their cognate binding sites.(A) Nucleosome depletion over factor sites increases with their proximity to, and with the strength of, boundaries. Shown is the combined nucleosome fold depletion over factor sites (y-axis) that are within a certain range of distances from boundaries that themselves have a particular nucleosome fold depletion (boundary strength; x-axis). Plots are shown for four different ranges of factor-boundary distances and for the four boundary strength groups of nucleosome fold depletions that we defined based on sequence rules (see Methods). (B) Factor binding sites near boundaries are depleted of nucleosomes. For each factor, shown is the combined nucleosome fold depletion over its annotated sites [47],[67] that are within 30 bp from a boundary whose fold depletion is at least 5 (blue bars), and over the rest of its sites (green bars). The combined fold depletion of a set of genomic elements is the ratio between their expected and observed nucleosome coverage (see Methods).

Mentions: We next asked whether nucleosome depletion over factor sites depends on the boundary strength and factor-boundary distances. Notably, the level of nucleosome depletion over factor sites increases significantly with both the strength of the boundary and its proximity to factor sites (Figure 10A). Specifically, for 50 of 51 factors for which more than 10 sites are annotated [47], we find stronger nucleosome depletion at the subset of its sites that are near boundaries compared to its other sites (Figure 10B). The only exception is Reb1, a highly abundant factor that possesses ATP-independent chromatin remodeling activity [48]. Taken together, our results demonstrate that boundaries enhance the accessibility of transcription factors to their cognate sites, by depleting nucleosomes from the adjacent DNA, with the magnitude of such depletion increasing with both the strength of the boundary and its proximity to the factor site.


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)

Boundaries enhance the accessibility of transcription factors to their cognate binding sites.(A) Nucleosome depletion over factor sites increases with their proximity to, and with the strength of, boundaries. Shown is the combined nucleosome fold depletion over factor sites (y-axis) that are within a certain range of distances from boundaries that themselves have a particular nucleosome fold depletion (boundary strength; x-axis). Plots are shown for four different ranges of factor-boundary distances and for the four boundary strength groups of nucleosome fold depletions that we defined based on sequence rules (see Methods). (B) Factor binding sites near boundaries are depleted of nucleosomes. For each factor, shown is the combined nucleosome fold depletion over its annotated sites [47],[67] that are within 30 bp from a boundary whose fold depletion is at least 5 (blue bars), and over the rest of its sites (green bars). The combined fold depletion of a set of genomic elements is the ratio between their expected and observed nucleosome coverage (see Methods).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000216-g010: Boundaries enhance the accessibility of transcription factors to their cognate binding sites.(A) Nucleosome depletion over factor sites increases with their proximity to, and with the strength of, boundaries. Shown is the combined nucleosome fold depletion over factor sites (y-axis) that are within a certain range of distances from boundaries that themselves have a particular nucleosome fold depletion (boundary strength; x-axis). Plots are shown for four different ranges of factor-boundary distances and for the four boundary strength groups of nucleosome fold depletions that we defined based on sequence rules (see Methods). (B) Factor binding sites near boundaries are depleted of nucleosomes. For each factor, shown is the combined nucleosome fold depletion over its annotated sites [47],[67] that are within 30 bp from a boundary whose fold depletion is at least 5 (blue bars), and over the rest of its sites (green bars). The combined fold depletion of a set of genomic elements is the ratio between their expected and observed nucleosome coverage (see Methods).
Mentions: We next asked whether nucleosome depletion over factor sites depends on the boundary strength and factor-boundary distances. Notably, the level of nucleosome depletion over factor sites increases significantly with both the strength of the boundary and its proximity to factor sites (Figure 10A). Specifically, for 50 of 51 factors for which more than 10 sites are annotated [47], we find stronger nucleosome depletion at the subset of its sites that are near boundaries compared to its other sites (Figure 10B). The only exception is Reb1, a highly abundant factor that possesses ATP-independent chromatin remodeling activity [48]. Taken together, our results demonstrate that boundaries enhance the accessibility of transcription factors to their cognate sites, by depleting nucleosomes from the adjacent DNA, with the magnitude of such depletion increasing with both the strength of the boundary and its proximity to the factor site.

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