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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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Our model predicts distinct nucleosome organizations around transcription start sites.Shown is the average nucleosome organization around transcription start sites of four sets of genes that were reported in [5] by clustering their measured nucleosome occupancy profiles. One of the four clusters reported in [5] corresponds to promoters that lack a significant nucleosome depleted region (cluster 1; red line in plots). The other three clusters have a clear nucleosome depleted region in their promoters, and are also reported in [5] as enriched for protein biosynthesis (cluster 2; green line), ribosome biogenesis (cluster 3; blue line), and protein modification (cluster 4; cyan line). The average nucleosome occupancy is shown from the original data of [5] (top) that was used for the clustering, and for our data (middle), as well as for the predicted occupancy of the nucleosome positioning model that we developed here (bottom).
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pcbi-1000216-g004: Our model predicts distinct nucleosome organizations around transcription start sites.Shown is the average nucleosome organization around transcription start sites of four sets of genes that were reported in [5] by clustering their measured nucleosome occupancy profiles. One of the four clusters reported in [5] corresponds to promoters that lack a significant nucleosome depleted region (cluster 1; red line in plots). The other three clusters have a clear nucleosome depleted region in their promoters, and are also reported in [5] as enriched for protein biosynthesis (cluster 2; green line), ribosome biogenesis (cluster 3; blue line), and protein modification (cluster 4; cyan line). The average nucleosome occupancy is shown from the original data of [5] (top) that was used for the clustering, and for our data (middle), as well as for the predicted occupancy of the nucleosome positioning model that we developed here (bottom).

Mentions: Recent analyses of genome-wide nucleosome occupancy measurements in yeast identified different classes of nucleosome occupancy patterns in gene promoters, by clustering the nucleosome occupancy patterns [5]. Notably, we find that our model is also able to accurately predict the occupancy patterns of these different classes, suggesting that these differing nucleosome occupancy patterns are partly encoded in the DNA sequence, through the nucleosome sequence preferences (Figure 4).


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)

Our model predicts distinct nucleosome organizations around transcription start sites.Shown is the average nucleosome organization around transcription start sites of four sets of genes that were reported in [5] by clustering their measured nucleosome occupancy profiles. One of the four clusters reported in [5] corresponds to promoters that lack a significant nucleosome depleted region (cluster 1; red line in plots). The other three clusters have a clear nucleosome depleted region in their promoters, and are also reported in [5] as enriched for protein biosynthesis (cluster 2; green line), ribosome biogenesis (cluster 3; blue line), and protein modification (cluster 4; cyan line). The average nucleosome occupancy is shown from the original data of [5] (top) that was used for the clustering, and for our data (middle), as well as for the predicted occupancy of the nucleosome positioning model that we developed here (bottom).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000216-g004: Our model predicts distinct nucleosome organizations around transcription start sites.Shown is the average nucleosome organization around transcription start sites of four sets of genes that were reported in [5] by clustering their measured nucleosome occupancy profiles. One of the four clusters reported in [5] corresponds to promoters that lack a significant nucleosome depleted region (cluster 1; red line in plots). The other three clusters have a clear nucleosome depleted region in their promoters, and are also reported in [5] as enriched for protein biosynthesis (cluster 2; green line), ribosome biogenesis (cluster 3; blue line), and protein modification (cluster 4; cyan line). The average nucleosome occupancy is shown from the original data of [5] (top) that was used for the clustering, and for our data (middle), as well as for the predicted occupancy of the nucleosome positioning model that we developed here (bottom).
Mentions: Recent analyses of genome-wide nucleosome occupancy measurements in yeast identified different classes of nucleosome occupancy patterns in gene promoters, by clustering the nucleosome occupancy patterns [5]. Notably, we find that our model is also able to accurately predict the occupancy patterns of these different classes, suggesting that these differing nucleosome occupancy patterns are partly encoded in the DNA sequence, through the nucleosome sequence preferences (Figure 4).

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