Integrating ChIP-seq with other functional genomics data

Transcription is regulated by transcription factor (TF) binding at promoters and distal regulatory elements and histone modifications that control the accessibility of these elements. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) has become the standard assay for identifying genome-wide protein–DNA interactions in vitro and in vivo. As large-scale ChIP-seq data sets have been collected for different TFs and histone modifications, their potential to predict gene expression can be used to test hypotheses about the mechanisms of gene regulation. In addition, complementary functional genomics assays provide a global view of chromatin accessibility and long-range cis-regulatory interactions that are being combined with TF binding and histone remodeling to study the regulation of gene expression. Thus, ChIP-seq analysis is now widely integrated with other functional genomics assays to better understand gene regulatory mechanisms. In this review, we discuss advances and challenges in integrating ChIP-seq data to identify context-specific chromatin states associated with gene activity. We describe the overall computational design of integrating ChIP-seq data with other functional genomics assays. We also discuss the challenges of extending these methods to low-input ChIP-seq assays and related single-cell assays.