This study presents a method to identify and predict tissue-specific enhancers in the human genome using chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq) of the enhancer-associated protein p300. The researchers mapped p300 binding sites in mouse embryonic forebrain, midbrain, and limb tissues, and tested 86 of these sequences in a transgenic mouse assay. The results showed that p300 binding accurately predicted the location and activity of enhancers in specific tissues, with a success rate of 87% for forebrain predictions, 88% for midbrain predictions, and 88% for limb predictions. This approach provides a highly accurate means for identifying enhancers and their activities, and has potential applications in studying tissue-specific enhancers in human biology and disease. The study also found that most p300-bound regions are under evolutionary constraint, overlapping conserved non-coding sequences, and are enriched near genes expressed in the same tissue.This study presents a method to identify and predict tissue-specific enhancers in the human genome using chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq) of the enhancer-associated protein p300. The researchers mapped p300 binding sites in mouse embryonic forebrain, midbrain, and limb tissues, and tested 86 of these sequences in a transgenic mouse assay. The results showed that p300 binding accurately predicted the location and activity of enhancers in specific tissues, with a success rate of 87% for forebrain predictions, 88% for midbrain predictions, and 88% for limb predictions. This approach provides a highly accurate means for identifying enhancers and their activities, and has potential applications in studying tissue-specific enhancers in human biology and disease. The study also found that most p300-bound regions are under evolutionary constraint, overlapping conserved non-coding sequences, and are enriched near genes expressed in the same tissue.