Cluster analysis of differential histone modification levels at transcriptional start sites reveals groups of co-regulated genes associated with immune-relevant functions.

<p>A) Heat map indicates result of un-supervised hierarchical clustering for 743 gene promoters with significant changes of at least one histone modification (absolute log2 (fold change) > = 1 and p<0.01). Depicted are the average z-scaled read counts (P: two patients; C: four controls) from a 2000 bp interval around the transcriptional start sites of RefSeq annotated transcripts. Rows indicate the data for the 743 genes. Dendrogram shows the relationship between individual genes. In total we identified 25 different clusters (separated by black boxes), exemplarily two clusters are indicated (grey shaded trapezoid). B) When comparing patients and controls the upper cluster (consisting of 86 genes) is characterized by decreased H3K4me3 and H3K9Ac binding as increased H3K27me3 binding (“silenced cluster”). Promoter specific differences are indicated by average histone modification profiles across all genes constituting the cluster (average binding shown; red: two patients; blue: four controls). The cluster is enriched for genes of the MHC complex and accordingly we identify related GO-terms to be significantly enriched for the genes of this cluster (bar plot shows -log10-transformed p-values derived from hypergeometric testing). C) When comparing patients and healthy controls the lower cluster (consisting of 43 genes) is characterized by increased H3K4me3 and H3K9ac binding and decreased H3K27me3 binding (“active cluster”). Promoter specific differences are indicated by average histone modification profiles across all genes constituting the cluster (average binding shown; red: two patients; blue: four controls). The cluster is enriched for genes related to immune response (bar plot shows -log10-transformed p-values derived from hypergeometric testing). In addition the cluster is enriched for genes related to the GO-term "chromatin assembly/ disassembly".