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First, ChIP-Seq tags represent only the ends of the ChIP fragments, instead of precise protein-DNA binding sites. While providing several advantages over ChIP-chip, such as less starting material, lower cost, and higher peak resolution, ChIP-Seq also poses challenges (or opportunities) in the analysis of data. Technologies such as Illumina's Solexa or Applied Biosystems' SOLiD™ have made ChIP-Seq a practical and potentially superior alternative to ChIP-chip. 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. Although early ChIP-Seq efforts were limited by sequencing throughput and cost, tremendous progress has been achieved in the past year in the development of next generation massively parallel sequencing. Chromatin immunoprecipitation (ChIP) coupled with genome tiling microarrays (ChIP-chip) and sequencing (ChIP-Seq) have become popular techniques to identify cistromes. The determination of the 'cistrome', the genome-wide set of in vivo cis-elements bound by trans-factors, is necessary to determine the genes that are directly regulated by those trans-factors.