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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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Combinatorial chromatin modification patterns associated with genomic features. (A) CpG islands; (B) enhancers (distal p300 binding sites); (C) insulators (CTCF binding sites); (D) promoters. Each cell in the heatmap represents the normalized co-occurrence frequency of a pair of chromatin modifications within the set of biclusters belonging to a specific class of genomic feature. Heatmaps are clustered using hierarchical clustering.
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Figure 5: Combinatorial chromatin modification patterns associated with genomic features. (A) CpG islands; (B) enhancers (distal p300 binding sites); (C) insulators (CTCF binding sites); (D) promoters. Each cell in the heatmap represents the normalized co-occurrence frequency of a pair of chromatin modifications within the set of biclusters belonging to a specific class of genomic feature. Heatmaps are clustered using hierarchical clustering.

Mentions: Next, we focused our analysis on four classes of genomic features that are most abundant in the genome: CpG islands, distal enhancers, insulators and promoters. Figure 5 depicts the co-occurrence maps for the chromatin marks associated with these genomic features. Co-occurrence maps for the remaining four classes of genomic features, i.e. conserved sequences, DHSs, lincRNAs and protein-coding genes, can be found in Supplementary Figures S6–S9.Figure 5.


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

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

Combinatorial chromatin modification patterns associated with genomic features. (A) CpG islands; (B) enhancers (distal p300 binding sites); (C) insulators (CTCF binding sites); (D) promoters. Each cell in the heatmap represents the normalized co-occurrence frequency of a pair of chromatin modifications within the set of biclusters belonging to a specific class of genomic feature. Heatmaps are clustered using hierarchical clustering.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 5: Combinatorial chromatin modification patterns associated with genomic features. (A) CpG islands; (B) enhancers (distal p300 binding sites); (C) insulators (CTCF binding sites); (D) promoters. Each cell in the heatmap represents the normalized co-occurrence frequency of a pair of chromatin modifications within the set of biclusters belonging to a specific class of genomic feature. Heatmaps are clustered using hierarchical clustering.
Mentions: Next, we focused our analysis on four classes of genomic features that are most abundant in the genome: CpG islands, distal enhancers, insulators and promoters. Figure 5 depicts the co-occurrence maps for the chromatin marks associated with these genomic features. Co-occurrence maps for the remaining four classes of genomic features, i.e. conserved sequences, DHSs, lincRNAs and protein-coding genes, can be found in Supplementary Figures S6–S9.Figure 5.

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