ChIP-seq Accurately Predicts Tissue-Specific Activity of Enhancers

Determining the spatial and temporal activity patterns of enhancers remains a challenge in the functional annotation of the human genome. Here, we performed genome-wide mapping of tissue-specific in vivo binding sites for the enhancer-associated protein p300 and assessed in transgenic mice the utility of this information in identifying enhancers and predicting their activity patterns. Chromatin immunoprecipitation followed by massively-parallel sequencing was used to identify p300-enriched sites in mouse embryonic day 11.5 (e11.5) forebrain, midbrain, and limb. In total, 4,686 genomic regions were enriched for p300 in vivo in at least one of these tissues. To determine whether p300-binding accurately identifies enhancers and predicts their activity patterns, we tested 86 of these regions in a transgenic mouse enhancer assay at e11.5. In 88% of the cases, p300-enriched sequences were reproducible enhancers, and in 91% of these cases p300 enrichment correctly predicted the tissues in which in vivo activity was observed. Our results indicate that in vivo mapping of p300 binding to non-coding DNA is a highly effective means for identifying enhancers and their associated spatial activity patterns. Overall design: Examination of p300 binding in 3 embryonic stage 11.5 mouse tissues