Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome

Recent investigations suggest that acetylation of various residues of histones H3 and H4 and trimethylation of Lys 4 of histone H3 (H3K4) in nucleosomes are characteristics of active promoters across species from yeast to mammals. Using chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) technology, these investigators mapped histone modifications, transcription factor binding, and nucleosome density in high resolution within 30 Mb of the human genome. It was found that active promoters are enriched with trimethylation of H3K4, whereas enhancers are marked by monomethylation of H3K4. These authors then incorporated these distinct chromatin signatures into computational algorithms. Over 200 promoters and 400 enhancers were predicted within the 30-Mb region with high sensitivity and specificity. To validate the prediction, a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2) predicted from the computational algorithms was confirmed with reporter assay (Fig. 1).