title: Protein-DNA binding in high-resolution.
abstract: Recent advances in experimental and computational methodologies are enabling ultra-high resolution genome-wide profiles of protein-DNA binding events. For example, the ChIP-exo protocol precisely characterizes protein-DNA cross-linking patterns by combining chromatin immunoprecipitation (ChIP) with 5' → 3' exonuclease digestion. Similarly, deeply sequenced chromatin accessibility assays (e.g. DNase-seq and ATAC-seq) enable the detection of protected footprints at protein-DNA binding sites. With these techniques and others, we have the potential to characterize the individual nucleotides that interact with transcription factors, nucleosomes, RNA polymerases and other regulatory proteins in a particular cellular context. In this review, we explain the experimental assays and computational analysis methods that enable high-resolution profiling of protein-DNA binding events. We discuss the challenges and opportunities associated with such approaches.
authors.affiliation: a Department of Biochemistry & Molecular Biology , Center for Eukaryotic Gene Regulation, The Pennsylvania State University , University Park , PA , USA.
authors.forename: Shaun
authors.initials: S
authors.lastname: Mahony
authors.affiliation: a Department of Biochemistry & Molecular Biology , Center for Eukaryotic Gene Regulation, The Pennsylvania State University , University Park , PA , USA.
authors.forename: B Franklin
authors.initials: BF
authors.lastname: Pugh
mesh_terms: D000818:Animals; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation / Q000639:trends; D019295:Computational Biology / Q000639:trends; D003198:Computer Simulation / Q000639:trends; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D018983:DNA Footprinting / Q000639:trends; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D066264:Datasets as Topic; D005090:Exodeoxyribonucleases / Q000378:metabolism; D005103:Expert Systems; D023281:Genomics / Q000379:methods / Q000639:trends; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D023302:Protein Footprinting / Q000639:trends
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D009707:Nucleosomes; D004247:DNA; D005090:Exodeoxyribonucleases
keywords: ChIP-exo; ChIP-seq; DNase-seq; high-resolution; protein–DNA binding; transcription factor binding