An integrated strategy for identification of both sharp and broad peaks from next-generation sequencing data

See research article: http://genomebiology.com/2011/12/7/r67Transcriptional regulation plays a central role in essential biological processes, including cellular differentiation and responses to cellular and environmental signals. It is becoming increasingly clear that transcription of a large number of genes is coordinately regulated during these processes through transcriptional regulatory networks consisting of three major components: (1) cis regulatory elements, including promoters and enhancers; (2) trans factors, including transcription factors (TFs) and chromatin modifying enzymes; and (3) chromatin modification states at regulatory regions of genes. Recent development of assays, including ChIP-Seq, DNase-Seq and FAIRE-Seq, which utilize next generation high-throughput sequencing, has propelled the advance in our understanding of these three components of transcriptional regulatory networks. Critical for application of these assays are a number of different algorithms that have been developed to identify signal-enriched regions (or peaks) from these genome-wide datasets, including the latest program reported by Rashid et al. in this issue of Genome Biology [1].Increasingly numerous datasets of genome-wide profiling of epigenetic modifications and chromatin-binding proteins are being generated. Depending on the distribution pattern of sequencing reads on the genome, there are virtually two kinds of signals: sharp and diffuse signals. While TFs generally recognize specific target motifs, either in enhancers or promoters, and exhibit localized strong signals, the distribution of histone-modification signals ranges from a few nucleosomes to large chromatin domains spanning hundreds of kilobases. For example, H3K4me2 and H3K4me3, which are usually associated with enhancers and promoters, tend to exhibit localized, sharp peaks, whereas H3K27me3, associated with gene silencing, may cover entire chromatin domains [2,3]. On yet larger scales, it is known that H3K9me3