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Combinatorial chromatin modification patterns in the human genome revealed by subspace clustering.

Ucar D, Hu Q, Tan K - Nucleic Acids Res. (2011)

Bottom Line: We identify 843 combinatorial patterns that recur at >0.1% of the genome.A total of 19 chromatin modifications are observed in the combinatorial patterns, 10 of which occur in more than half of the patterns.We also identify combinatorial modification signatures for eight classes of functional DNA elements.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Iowa, Iowa City, 52242 Iowa, USA.

ABSTRACT
Chromatin modifications, such as post-translational modification of histone proteins and incorporation of histone variants, play an important role in regulating gene expression. Joint analyses of multiple histone modification maps are starting to reveal combinatorial patterns of modifications that are associated with functional DNA elements, providing support to the 'histone code' hypothesis. However, due to the lack of analytical methods, only a small number of chromatin modification patterns have been discovered so far. Here, we introduce a scalable subspace clustering algorithm, coherent and shifted bicluster identification (CoSBI), to exhaustively identify the set of combinatorial modification patterns across a given epigenome. Performance comparisons demonstrate that CoSBI can generate biclusters with higher intra-cluster coherency and biological relevance. We apply our algorithm to a compendium of 39 genome-wide chromatin modification maps in human CD4(+) T cells. We identify 843 combinatorial patterns that recur at >0.1% of the genome. A total of 19 chromatin modifications are observed in the combinatorial patterns, 10 of which occur in more than half of the patterns. We also identify combinatorial modification signatures for eight classes of functional DNA elements. Application of CoSBI to epigenome maps of different cells and developmental stages will aid in understanding how chromatin structure helps regulate gene expression.

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Predicted biclusters supported by mass spectrometry data. Shown is the cumulative distribution of predicted biclusters whose histone modification members are supported by mass spectrometry data.
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Figure 3: Predicted biclusters supported by mass spectrometry data. Shown is the cumulative distribution of predicted biclusters whose histone modification members are supported by mass spectrometry data.

Mentions: The biclusters predicted by CoSBI are based on histone modification generated using ChIP-Seq technology. An alternative experimental protocol for identifying combinatorial histone modifications is tandem mass spectrometry (MS) (29). Compared to ChIP-based method, the major advantage of MS is that it can detect all modifications associated with a given histone tail simultaneously. As a first means to corroborate our predicted biclusters, we have manually compiled a list of 366 unique combinatorial histone modifications, each of which is observed in a single histone tail using MS (Supplementary Table S3). As shown in Figure 3, for 50% of the predicted biclusters, 40% of their member histone marks are also observed in a single histone tail in the mass spectrometry experiments. Note that this curated list of histone codes only involves histones H3 and H4. Since our biclusters also involve histone H2, the fraction of supported bicluster members will be even higher when MS data on H2 become available in the future.Figure 3.


Combinatorial chromatin modification patterns in the human genome revealed by subspace clustering.

Ucar D, Hu Q, Tan K - Nucleic Acids Res. (2011)

Predicted biclusters supported by mass spectrometry data. Shown is the cumulative distribution of predicted biclusters whose histone modification members are supported by mass spectrometry data.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105409&req=5

Figure 3: Predicted biclusters supported by mass spectrometry data. Shown is the cumulative distribution of predicted biclusters whose histone modification members are supported by mass spectrometry data.
Mentions: The biclusters predicted by CoSBI are based on histone modification generated using ChIP-Seq technology. An alternative experimental protocol for identifying combinatorial histone modifications is tandem mass spectrometry (MS) (29). Compared to ChIP-based method, the major advantage of MS is that it can detect all modifications associated with a given histone tail simultaneously. As a first means to corroborate our predicted biclusters, we have manually compiled a list of 366 unique combinatorial histone modifications, each of which is observed in a single histone tail using MS (Supplementary Table S3). As shown in Figure 3, for 50% of the predicted biclusters, 40% of their member histone marks are also observed in a single histone tail in the mass spectrometry experiments. Note that this curated list of histone codes only involves histones H3 and H4. Since our biclusters also involve histone H2, the fraction of supported bicluster members will be even higher when MS data on H2 become available in the future.Figure 3.

Bottom Line: We identify 843 combinatorial patterns that recur at >0.1% of the genome.A total of 19 chromatin modifications are observed in the combinatorial patterns, 10 of which occur in more than half of the patterns.We also identify combinatorial modification signatures for eight classes of functional DNA elements.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Iowa, Iowa City, 52242 Iowa, USA.

ABSTRACT
Chromatin modifications, such as post-translational modification of histone proteins and incorporation of histone variants, play an important role in regulating gene expression. Joint analyses of multiple histone modification maps are starting to reveal combinatorial patterns of modifications that are associated with functional DNA elements, providing support to the 'histone code' hypothesis. However, due to the lack of analytical methods, only a small number of chromatin modification patterns have been discovered so far. Here, we introduce a scalable subspace clustering algorithm, coherent and shifted bicluster identification (CoSBI), to exhaustively identify the set of combinatorial modification patterns across a given epigenome. Performance comparisons demonstrate that CoSBI can generate biclusters with higher intra-cluster coherency and biological relevance. We apply our algorithm to a compendium of 39 genome-wide chromatin modification maps in human CD4(+) T cells. We identify 843 combinatorial patterns that recur at >0.1% of the genome. A total of 19 chromatin modifications are observed in the combinatorial patterns, 10 of which occur in more than half of the patterns. We also identify combinatorial modification signatures for eight classes of functional DNA elements. Application of CoSBI to epigenome maps of different cells and developmental stages will aid in understanding how chromatin structure helps regulate gene expression.

Show MeSH
Related in: MedlinePlus