DHSs overlap orthogonally-measured functional regulatory elements. (a) DHS locations correlate with functional regulatory sites from orthogonal datasets. Pie chart depicting the percentage of all DHSs identified across all stages in non-coding sequence (n = 35,769 at FDR 1%) that overlap the binding locations of other factors: CTCF, ORC, and/or any 1 of 21 developmental transcription factors. (b) DHSs are enriched at transcription start sites (TSSs) relative to genomic feature percentage. The bar graph depicts the percentage of all 1% FDR DHSs identified across all stages whose central nucleotides are located within 100 bp of a TSS, or in 5' UTRs, coding sequences, introns, 3' UTRs or between genes (intergenic). (c) Core promoter composition directs temporal changes in accessibility of TSSs. The peak in DNase I cleavage density was determined for each stage at the -60 to +40 regions of each promoter, and was clustered using kmeans. The average peak density at each stage and for each cluster is shown at left in a spectrum from yellow (high) to blue (low), forming two metaclusters: one that is constitutively high or exhibits a decrease in accessibility during development (top panels), and another set of promoters that exhibit increasing accessibility during development (bottom panels). For each cluster, the relative enrichments of each of six previously identified core promoter motifs found in each cluster are shown in a spectrum from red (high) to white (low), with the sequence logos for each motif presented on the right. Three motifs, the DNA replication-related element (DREF), r1 and r7, were greatly enriched within constitutive/down-regulated promoters, while the downstream promoter element (DPE), the initiator (INR), and MTE (motif ten element) were enriched in the upregulated promoters. (d) Different promoter classes exhibit distinct structural morphologies. Chromatin accessibility in terms of mean DNaseI tag density was plotted within a 1-kb window of the TSS for clusters indicated as (i) and (ii) in panel (c). Chromatin accessibility for stage 5 is shown in green and that for stage 14 in purple. In addition to the developmental profiling of these promoters, (i) shows a distinct double-peaked pattern that is different from the patterns of DNaseI cleavage around other promoter types.
Thomas et al. Genome Biology 2011 12:R43 doi:10.1186/gb-2011-12-5-r43