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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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Type I and Type II promoters have distinct architectures.(A) Shown is a schematic illustration of promoter architectures for the two extreme types of promoters from Figure 11A. The schematic illustrates that in the high noise (Type I, left column) promoters, factor binding sites are measurably occupied by both their cognate factors and nucleosomes (in a cell population), suggesting that their high noise results from competition between nucleosomes and factors for DNA access. In contrast, the low noise (Type II, right column) promoters exhibit a characteristic nucleosome-depleted region upstream of the transcription start site in which bound factor sites are highly concentrated. Also shown is the average number of nucleosome reads in our data (cyan), and the distribution of factor sites (brown) and TATA elements (green, only for Type I promoters), around the transcription start site of the genes in each of the two extreme types of promoters from (A) (left column, Type I promoters; right column, Type II promoters). (B) Genes of the high- and low-noise promoter classes exhibit distinct functional enrichments. Shown is a selected list of functional categories that are significantly enriched (P<10−5) in the set of genes associated with each promoter type (see Figure S7 for the full list and details of all enrichments). (C) The distinct nucleosome organizations in high- and low-noise promoters can be predicted from DNA sequence. Shown is the average nucleosome occupancy predicted by the sequence-based model for nucleosome positioning that we developed here, for each of the two promoter types in (A).
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pcbi-1000216-g012: Type I and Type II promoters have distinct architectures.(A) Shown is a schematic illustration of promoter architectures for the two extreme types of promoters from Figure 11A. The schematic illustrates that in the high noise (Type I, left column) promoters, factor binding sites are measurably occupied by both their cognate factors and nucleosomes (in a cell population), suggesting that their high noise results from competition between nucleosomes and factors for DNA access. In contrast, the low noise (Type II, right column) promoters exhibit a characteristic nucleosome-depleted region upstream of the transcription start site in which bound factor sites are highly concentrated. Also shown is the average number of nucleosome reads in our data (cyan), and the distribution of factor sites (brown) and TATA elements (green, only for Type I promoters), around the transcription start site of the genes in each of the two extreme types of promoters from (A) (left column, Type I promoters; right column, Type II promoters). (B) Genes of the high- and low-noise promoter classes exhibit distinct functional enrichments. Shown is a selected list of functional categories that are significantly enriched (P<10−5) in the set of genes associated with each promoter type (see Figure S7 for the full list and details of all enrichments). (C) The distinct nucleosome organizations in high- and low-noise promoters can be predicted from DNA sequence. Shown is the average nucleosome occupancy predicted by the sequence-based model for nucleosome positioning that we developed here, for each of the two promoter types in (A).

Mentions: We further examined those promoters having TATA elements and nucleosome-covered factor binding sites, and those promoters lacking TATA elements and having nucleosome-depleted factor binding sites, since these promoter sets are the most and least noisy promoters, respectively (Figure 11A), and they each have more genes than would be expected (Figure 11B). Intriguingly, in addition to their differential noise, we also find distinct promoter architectures and nucleosome dynamics in these two promoter types. Type I promoters, which contain TATA elements and whose sites are nucleosome-covered, have many factor sites spread across the promoter region, a weaker signal of nucleosome depletion at the typical nucleosome depleted region (NDR), and are enriched in targets of condition-specific factors and non-essential genes (Figure 12A and 12B and Figure S7). These promoters are targets of chromatin remodeling complexes [54] and their rate of histone turnover [55] is significantly high (Figure 11C), consistent with an ongoing dynamic competition between nucleosome assembly and factor binding. In contrast, type II promoters, which are TATA-less and whose sites are nucleosome-depleted, have strong nucleosome depletion, many boundary elements at the typical NDR, low histone turnover, and an overall smaller number of factor sites but with a high preference for these sites to be located at the NDR (Figure 12A). Type II promoters are enriched in essential genes and in ribosomal protein genes, the latter presumably owing to the fact that these proteins are highly expressed and are required stoichiometrically in a large complex, thereby conferring a benefit to regulation with low noise (Figure 12B).


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)

Type I and Type II promoters have distinct architectures.(A) Shown is a schematic illustration of promoter architectures for the two extreme types of promoters from Figure 11A. The schematic illustrates that in the high noise (Type I, left column) promoters, factor binding sites are measurably occupied by both their cognate factors and nucleosomes (in a cell population), suggesting that their high noise results from competition between nucleosomes and factors for DNA access. In contrast, the low noise (Type II, right column) promoters exhibit a characteristic nucleosome-depleted region upstream of the transcription start site in which bound factor sites are highly concentrated. Also shown is the average number of nucleosome reads in our data (cyan), and the distribution of factor sites (brown) and TATA elements (green, only for Type I promoters), around the transcription start site of the genes in each of the two extreme types of promoters from (A) (left column, Type I promoters; right column, Type II promoters). (B) Genes of the high- and low-noise promoter classes exhibit distinct functional enrichments. Shown is a selected list of functional categories that are significantly enriched (P<10−5) in the set of genes associated with each promoter type (see Figure S7 for the full list and details of all enrichments). (C) The distinct nucleosome organizations in high- and low-noise promoters can be predicted from DNA sequence. Shown is the average nucleosome occupancy predicted by the sequence-based model for nucleosome positioning that we developed here, for each of the two promoter types in (A).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000216-g012: Type I and Type II promoters have distinct architectures.(A) Shown is a schematic illustration of promoter architectures for the two extreme types of promoters from Figure 11A. The schematic illustrates that in the high noise (Type I, left column) promoters, factor binding sites are measurably occupied by both their cognate factors and nucleosomes (in a cell population), suggesting that their high noise results from competition between nucleosomes and factors for DNA access. In contrast, the low noise (Type II, right column) promoters exhibit a characteristic nucleosome-depleted region upstream of the transcription start site in which bound factor sites are highly concentrated. Also shown is the average number of nucleosome reads in our data (cyan), and the distribution of factor sites (brown) and TATA elements (green, only for Type I promoters), around the transcription start site of the genes in each of the two extreme types of promoters from (A) (left column, Type I promoters; right column, Type II promoters). (B) Genes of the high- and low-noise promoter classes exhibit distinct functional enrichments. Shown is a selected list of functional categories that are significantly enriched (P<10−5) in the set of genes associated with each promoter type (see Figure S7 for the full list and details of all enrichments). (C) The distinct nucleosome organizations in high- and low-noise promoters can be predicted from DNA sequence. Shown is the average nucleosome occupancy predicted by the sequence-based model for nucleosome positioning that we developed here, for each of the two promoter types in (A).
Mentions: We further examined those promoters having TATA elements and nucleosome-covered factor binding sites, and those promoters lacking TATA elements and having nucleosome-depleted factor binding sites, since these promoter sets are the most and least noisy promoters, respectively (Figure 11A), and they each have more genes than would be expected (Figure 11B). Intriguingly, in addition to their differential noise, we also find distinct promoter architectures and nucleosome dynamics in these two promoter types. Type I promoters, which contain TATA elements and whose sites are nucleosome-covered, have many factor sites spread across the promoter region, a weaker signal of nucleosome depletion at the typical nucleosome depleted region (NDR), and are enriched in targets of condition-specific factors and non-essential genes (Figure 12A and 12B and Figure S7). These promoters are targets of chromatin remodeling complexes [54] and their rate of histone turnover [55] is significantly high (Figure 11C), consistent with an ongoing dynamic competition between nucleosome assembly and factor binding. In contrast, type II promoters, which are TATA-less and whose sites are nucleosome-depleted, have strong nucleosome depletion, many boundary elements at the typical NDR, low histone turnover, and an overall smaller number of factor sites but with a high preference for these sites to be located at the NDR (Figure 12A). Type II promoters are enriched in essential genes and in ribosomal protein genes, the latter presumably owing to the fact that these proteins are highly expressed and are required stoichiometrically in a large complex, thereby conferring a benefit to regulation with low noise (Figure 12B).

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