Figure 4. Fine-scale CR binding profiles distinguish coherent gene sets.

(A) Combinatorial binding patterns of CRs at individual promoters are associated with distinct expression and function. Fine-scale binding profiles are shown for CRs (vertical sections) across 1,081 target promoters (rows) after hierarchical clustering and re-ordering of major promoter clusters based on expression (original ordering shown in Figure S3). The profiles depict enrichment Z-scores (red – high, white – low) for 300 bp windows within 3 kb of TSSs. Promoter clusters derived based on common CR binding profiles (indicated by thick white horizontal lines) share transcriptional status, and the corresponding genes often share coherent functions (labels on right, curated from enriched functional gene sets, listed in Table S4B). Left bar shows RNA expression levels (log₂(FPKM)) derived from RNA-seq data: orange – high; blue – low; white – median. CR labels colored according to the dendrogram shown above. (B–D) Composite profiles for CRs with similar binding patterns at shared promoters. Profiles reflect average binding of the indicated CRs (Y axis) over co-bound promoters, centered on TSSs (X axis). (B) Peaks that surround TSSs, but dip at the TSS itself for CHD1 (purple) and SIRT6 (blue). (C) Sharp peaks over TSSs for HDAC2 (purple), PHF8 (green) and SAP30 (blue). (D) bimodal peaks of Polycomb CRs – diffuse peaks over TSSs for PRC2 members EZH2 (purple) and SUZ12 (blue) along with TSS-excluded peaks for PRC1 members CBX2 (green) and CBX8 (brown). (E) Composite profiles for CRs with distinct binding patterns at shared promoters. PLU1 (purple) has a sharp peak over TSSs, while CHD1 (blue) has a broader peak that extends downstream. Note that the promoters in this composite differ from panel B. (F–G) Composite profiles show distinct patterns for the same CR at promoter sets with different activity levels. (F) HDAC2 at PRC2-repressed (blue) and transcriptionally–competent promoters (purple). (G) HDAC1 at transcriptionally-competent (cluster 5, purple) and active (cluster 1, blue) promoters.