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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 organization at two genomic regions.Shown are the raw data measured in this study at two 1000bp-long genomic regions. Every cyan oval represents the genomic location of one nucleosome that we sequenced in its entirety. Also shown is the average nucleosome occupancy per basepair predicted by the sequence-based nucleosome model that we developed here (red), the raw hybridization signal of two microarray-based nucleosome maps [5],[10] (green and purple traces), and the locations of nucleosomes that were computationally inferred from these hybridization signals [5],[10] (green and purple ovals). Note that although the nucleosome calls from the microarray maps are close to nucleosome locations from our map, the microarray map does not reveal the underlying variability in the detailed nucleosome read locations that we observe in our data. Annotated genes [63], transcription factor binding sites [47], TATA sequences [53], and Poly(dA:dT) elements in the region are also shown (top).
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pcbi-1000216-g001: Nucleosome organization at two genomic regions.Shown are the raw data measured in this study at two 1000bp-long genomic regions. Every cyan oval represents the genomic location of one nucleosome that we sequenced in its entirety. Also shown is the average nucleosome occupancy per basepair predicted by the sequence-based nucleosome model that we developed here (red), the raw hybridization signal of two microarray-based nucleosome maps [5],[10] (green and purple traces), and the locations of nucleosomes that were computationally inferred from these hybridization signals [5],[10] (green and purple ovals). Note that although the nucleosome calls from the microarray maps are close to nucleosome locations from our map, the microarray map does not reveal the underlying variability in the detailed nucleosome read locations that we observe in our data. Annotated genes [63], transcription factor binding sites [47], TATA sequences [53], and Poly(dA:dT) elements in the region are also shown (top).

Mentions: After excluding nucleosomes that map to repetitive regions, we obtained ∼380,000 uniquely mapped nucleosomes such that on average, every basepair is covered by five nucleosome reads (Figure 1). To validate our nucleosome map, we compared it to ∼100 nucleosome positions mapped using conventional sequencing [2], three large collections of generic nucleosomes mapped using microarrays [5],[9],[10], and two collections of generic [11] and H2A.Z [13] nucleosomes mapped by sequencing one end of each nucleosome. Our map shows significant correspondence with all existing maps but differs in both the detailed locations and occupancy of many measured nucleosomes (Figure S1).


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 organization at two genomic regions.Shown are the raw data measured in this study at two 1000bp-long genomic regions. Every cyan oval represents the genomic location of one nucleosome that we sequenced in its entirety. Also shown is the average nucleosome occupancy per basepair predicted by the sequence-based nucleosome model that we developed here (red), the raw hybridization signal of two microarray-based nucleosome maps [5],[10] (green and purple traces), and the locations of nucleosomes that were computationally inferred from these hybridization signals [5],[10] (green and purple ovals). Note that although the nucleosome calls from the microarray maps are close to nucleosome locations from our map, the microarray map does not reveal the underlying variability in the detailed nucleosome read locations that we observe in our data. Annotated genes [63], transcription factor binding sites [47], TATA sequences [53], and Poly(dA:dT) elements in the region are also shown (top).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000216-g001: Nucleosome organization at two genomic regions.Shown are the raw data measured in this study at two 1000bp-long genomic regions. Every cyan oval represents the genomic location of one nucleosome that we sequenced in its entirety. Also shown is the average nucleosome occupancy per basepair predicted by the sequence-based nucleosome model that we developed here (red), the raw hybridization signal of two microarray-based nucleosome maps [5],[10] (green and purple traces), and the locations of nucleosomes that were computationally inferred from these hybridization signals [5],[10] (green and purple ovals). Note that although the nucleosome calls from the microarray maps are close to nucleosome locations from our map, the microarray map does not reveal the underlying variability in the detailed nucleosome read locations that we observe in our data. Annotated genes [63], transcription factor binding sites [47], TATA sequences [53], and Poly(dA:dT) elements in the region are also shown (top).
Mentions: After excluding nucleosomes that map to repetitive regions, we obtained ∼380,000 uniquely mapped nucleosomes such that on average, every basepair is covered by five nucleosome reads (Figure 1). To validate our nucleosome map, we compared it to ∼100 nucleosome positions mapped using conventional sequencing [2], three large collections of generic nucleosomes mapped using microarrays [5],[9],[10], and two collections of generic [11] and H2A.Z [13] nucleosomes mapped by sequencing one end of each nucleosome. Our map shows significant correspondence with all existing maps but differs in both the detailed locations and occupancy of many measured nucleosomes (Figure S1).

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
Related in: MedlinePlus