Integrating ChIP-seq with other functional genomics data

Abstract

Transcription is regulated by transcription factor (TF) binding at promoters and distal regulatory elements and histonemodifications 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 ChIPseq data sets have been collected for different TFs and histonemodifications, their potential to predict gene expression can be used to test hypotheses about themechanisms 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 regulatorymechanisms. 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 thesemethods to low-input ChIP-seq assays and related single-cell assays.