GC skew defines distinct RNA polymerase pause sites in CpG island promoters

Pol II pausing correlates with GC skew. (A) MEME-ChIP was performed on the 100-bp sequence underlying the proximal pause and the distal pause for the promoters in each pausing class (distal, proximal, silent). An enrichment of G-rich sequences correlates with the predominant Pol II pause point for each class. (B) Heatmap representation of GC skew. The degree of GC skew was calculated in 20-bp bins. CGI promoters from the three classes are oriented and sorted by the distance from the TSS to the downstream CGI edge using the same sort order as Figure 1C. (C) Average GC skew across the three different pausing classes. CGI-associated promoters were oriented, and the distances from the TSS to the upstream and downstream CGI edge were independently scaled and anchored to the TSS (arrow). An additional 800 bases to either side of the CGI (unscaled) is included. (D,E) MCF7 cell GRO-seq sense tag density around the TSS (arrow) or the downstream edge of the CGI (±3 kb). All CGI promoters were sorted by decreasing GC skew for the 100 bases underlying the distal pause (D) or the proximal pause (E).