The determination of the 'cistrome', the genome-wide set of in vivo cis-elements bound by trans-factors [1], is necessary to determine the genes that are directly regulated by those trans-factors. Chromatin immunoprecipitation (ChIP) [2] coupled with genome tiling microarrays (ChIP-chip) [3,4] and sequencing (ChIP-Seq) [5-8] have become popular techniques to identify cistromes. Although early ChIP-Seq efforts were limited by sequencing throughput and cost [2,9], tremendous progress has been achieved in the past year in the development of next generation massively parallel sequencing. Tens of millions of short tags (25-50 bases) can now be simultaneously sequenced at less than 1% the cost of traditional Sanger sequencing methods. Technologies such as Illumina's Solexa or Applied Biosystems' SOLiD™ have made ChIP-Seq a practical and potentially superior alternative to ChIP-chip [5,8].
