ABSTRACT

Protein-DNA interactions play a crucial role in many major cellular processes, e.g. transcription, DNA replication, DNA repair, DNA recombination, and genome packaging. It is therefore vitally important to know the genomic location of these interactions in order to fully understand the mechanisms involved. Many in vitro and in vivo assays have been developed to determine the level and position of protein association with DNA. One such method is chromatin immunoprecipitation (ChIP; reviewed by Orlando, 2000). ChIP is a versatile technique that can be used to determine the position and strength of protein-DNA interactions in vivo. ChIP can also be coupled with microarray analysis: ChIP-chip (also known as ChIP-onchip or ChIP2). ChIP-chip allows identification of all protein-DNA interactions for a given protein on a genome-wide level. In principle, ChIP-chip can be used to map the genome-wide location of any protein that associates with DNA. This rapidly emerging technique has greatly advanced our understanding of a number of important cellular processes, including transcription (Lee et al., 2002; Harbison et al., 2004), DNA replication (Wyrick et al., 2001; Katou et al., 2003) and genome packaging (Bernstein et al., 2004; Glynn et al., 2004; Lee et al., 2004; Sekinger et al., 2005). Related techniques have also been used to study the association of proteins with RNA in vivo (Takizawa et al., 2000; Hieronymus and Silver, 2003; Shepard et al., 2003; Zhang et al., 2003) and of proteins with DNA in vitro (Mukherjee et al., 2004; Liu et al., 2005).