Sequence motif analysis for FAIREs marked by active histone modifications
As many FAIRE regulatory elements were linked with active histone modifications, we explored the possible existence of functional sequence motifs for known transcription factors in FAIRE-H3K4me3 and FAIRE-H3K9/14ac sites. The binding motifs, such as CTCF, MYB, GFY-staf, ETS, and NRF1, were common in both FAIRE-H3K4me3 and FAIRE-H3K9/14ac sites (Fig. 3A). However, NFY and RUNX motifs existed only in FAIRE-H3K4me3 sites, and the GATA3 motif was specifically detected in FAIRE-H3K9/14ac sites. For FAIRE-H3K4me1 sites, AP-1/2, NF1, CTCF, AP-2, FOXA1, USF1, and MAFA motifs were identified (Fig. 3B). Interestingly, the CTCF motif was commonly found in FAIRE-H3K4me1, FAIRE-H3K4me3, and FAIRE-H3K9/14ac. The genomewide positioning of regulatory elements marked by histone modifications is illustrated in a Venn diagram (Fig. 3C-3E). More than 60% of the FAIRE-H3K4me3 and FAIRE-H3K9/14ac regions carrying binding motifs were distributed at gene promoters; over 20% in the gene body; and at small portions far upstream of promoters (Fig. 3D and 3E). In contrast, the population of FAIRE-H3K4me1 was highly enriched in gene body regions (66.4%) as well as upstream of promoters (31.3%) but almost negligible at promoters (2.3%) (Fig. 3C).