Table 1.

Various techniques used to analyze transcription factor interactions with DNA, along with their benefits and shortcomings. This list is not meant to be exhaustive

Technique	Detects...	Benefits	Drawbacks	References
Nitrocellulose membrane binding assay Electrophoretic mobility shift assay	In vitro interaction between protein and ‘naked’ DNA	Simple and convenient Can discriminate between direct and indirect interactions	Not conclusive of in vivo interactions Low throughput	Damm et al. (1989) and Umesono et al. (1991)
DNase footprinting	Protein interaction with DNA at high resolution	Nucleotide level resolution allows precise identification of binding sites or nucleosome occupancy	In vitro assays are low throughput and are not conclusive of in vivo functionality In vivo approaches cannot identify bound protein	Payvar et al. (1983) and Gross & Garrard (1988)
Reporter assay	Ability of specific DNA sequence to activate, enhance, or repress transcription	Indicates transcriptional functionality of the DNA sequence in question	Sequence is placed out of context and may not reflect in vivo properties	Umesono et al. (1991)
Chromatin immunoprecipitation (ChIP)	Presence of specific protein at a specific location in vivo	In vivo system Allows observation of highly dynamic events	Requires a population of cells, so observations are not necessarily concurrent in a single cell Cannot directly indicate functional significance Interactions may be indirect	Orlando (2000) and Collas (2010)
ChIP–reChIP	Co-localization of two proteins at a specific genomic locus	Highly suggestive of functional relationship between two proteins at the chromatin level	Reduced signal to noise ratio Requires high quality antibodies	Furlan-Magaril et al. (2009)
μChIP	Presence of a specific protein and a specific location in vivo with as few as 100 cells	Low amount of starting material	Requires high-quality antibodies and high abundance protein	Collas (2010)
ChIP-chip ChIP-seq	Presence of a specific protein throughout a large portion or the entire genome	High throughput	Considerable variation between experiments Highly dependent on the quality of antibody Cannot directly indicate functional significance	Collas (2010)
ChIA–PET	Chromatin looping and interaction of distal loci of the genome due to a protein of interest	Identifies chromatin looping associated with protein of interest	Cannot demonstrate whether looping depends on the protein of interest Low signal to noise ratio	de Wit & de Laat (2012)