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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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Occurrence and co-occurrence frequencies of chromatin modification marks of CoSBI biclusters. (A) Occurrence frequency of chromatin modifications observed in biclusters and across the genome. (B) Hierarchical clustering of co-occurrence matrix for all chromatin modification pairs observed in biclusters.
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Figure 4: Occurrence and co-occurrence frequencies of chromatin modification marks of CoSBI biclusters. (A) Occurrence frequency of chromatin modifications observed in biclusters and across the genome. (B) Hierarchical clustering of co-occurrence matrix for all chromatin modification pairs observed in biclusters.

Mentions: Out of the 39 chromatin modifications we examined, only 19 are present in the identified biclusters. Their occurrence frequencies are depicted in Figure 4A. This set of chromatin marks includes all 17 backbone modifications that were identified by Wang et al. (3) (H2A.Z, H2BK5ac, H2BK12ac, H2BK20ac, H2BK120ac, H3K4ac, H3K9ac, H3K18ac, H3K27ac, H3K36ac, H4K5ac, H4K8ac, H4K91ac, H3K4me1, H3K4me2, H3K4me3 and H3K9me1) and two additional acetylations (H4K16ac and H4K12ac). Based on our frequency analysis (Figure 4A), we found that the following 10 chromatin modifications (H2BK5ac, H2BK120ac, H3K4ac, H3K9ac, H3K18ac, H3K27ac, H3K36ac, H4K5ac, H4K8ac and H3K4me3) along with the histone invariant H2AZ are very prone to participate in combinatorial patterns. Each of them occurred in more than half of the biclusters. This high tendency to participate in combinatorial patterns is not due to higher sequencing coverage of these marks. As can be seen in Figure 4A, the occurrence frequencies in CoSBI biclusters and overall occurrence frequencies in the genome are not correlated (Pearson’s correlation coefficient = 0.13). Overall occurrence frequency for a histone mark is computed as the ratio of ChIP-seq peaks identified by MACS and the total number of 5 kbp non-overlapping windows in the genome.Figure 4.


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

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

Occurrence and co-occurrence frequencies of chromatin modification marks of CoSBI biclusters. (A) Occurrence frequency of chromatin modifications observed in biclusters and across the genome. (B) Hierarchical clustering of co-occurrence matrix for all chromatin modification pairs observed in biclusters.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 4: Occurrence and co-occurrence frequencies of chromatin modification marks of CoSBI biclusters. (A) Occurrence frequency of chromatin modifications observed in biclusters and across the genome. (B) Hierarchical clustering of co-occurrence matrix for all chromatin modification pairs observed in biclusters.
Mentions: Out of the 39 chromatin modifications we examined, only 19 are present in the identified biclusters. Their occurrence frequencies are depicted in Figure 4A. This set of chromatin marks includes all 17 backbone modifications that were identified by Wang et al. (3) (H2A.Z, H2BK5ac, H2BK12ac, H2BK20ac, H2BK120ac, H3K4ac, H3K9ac, H3K18ac, H3K27ac, H3K36ac, H4K5ac, H4K8ac, H4K91ac, H3K4me1, H3K4me2, H3K4me3 and H3K9me1) and two additional acetylations (H4K16ac and H4K12ac). Based on our frequency analysis (Figure 4A), we found that the following 10 chromatin modifications (H2BK5ac, H2BK120ac, H3K4ac, H3K9ac, H3K18ac, H3K27ac, H3K36ac, H4K5ac, H4K8ac and H3K4me3) along with the histone invariant H2AZ are very prone to participate in combinatorial patterns. Each of them occurred in more than half of the biclusters. This high tendency to participate in combinatorial patterns is not due to higher sequencing coverage of these marks. As can be seen in Figure 4A, the occurrence frequencies in CoSBI biclusters and overall occurrence frequencies in the genome are not correlated (Pearson’s correlation coefficient = 0.13). Overall occurrence frequency for a histone mark is computed as the ratio of ChIP-seq peaks identified by MACS and the total number of 5 kbp non-overlapping windows in the genome.Figure 4.

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