ChIP-chip: considerations for the design, analysis, and application of genome-wide chromatin immunoprecipitation experiments

Chromatin immunoprecipitation (ChIP) is a well-established procedure used to investigate interactions between proteins and DNA. Coupled with whole-genome DNA microarrays, ChlPs allow one to determine the entire spectrum of in vivo DNA binding sites for any given protein. The design and analysis of ChIP-microarray (also called ChIP-chip) experiments differ significantly from the conventions used for more traditional microarray experiments that measure relative transcript levels. Furthermore, fundamental differences exist between single-locus ChIP approaches and ChlP-chip experiments, and these differences require new methods of analysis. In this light, we review the design of DNA microarrays, the selection of controls, the level of repetition required, and other critical parameters for success in the design and analysis of ChIP-chip experiments, especially those conducted in the context of mammalian or other relatively large genomes. (C) 2004 Elsevier Inc. All rights reserved.