Identification of epigenomic patterns to annotate regulatory elements in the human genome

Abstract

Recently, studies on transcriptional regulation have turned from single-gene to genome-wide research. This transgression provides new possibilities towards the identification of transcriptional regulation pathways, and the identification of new transcriptional regulatory elements. Recent technological advances have enabled the identification of histone modifications. These have been mapped to specific chromatin structures and transcriptional regulatory elements, such as promoters or enhancers. Specific patterns of histone modifications, regulatory proteins or chromatin structural properties have been discovered. These patterns were shown to demarcate specific regulatory elements, and are being increasingly used to identify novel elements. The resulting data from these studies show an intricate interplay between posttranslational histone modifications, chromatin structure, and genome function throughout different cellular conditions. It is considered that histone modification patterns enable prediction of functional regulatory elements, gene expression and splicing patterns. Increased knowledge on these patterns has facilitated research on different genomic expression profiles between healthy and diseased cells in many disorders and diseases. Many studies on cancer have indicated an important role for epigenetic regulation during cancer development, commending the important role of the search for epigenetic patterns and their potential function. Clear histone modification patterns have been identified for coding regions, promoters and enhancers. The negative regulatory elements, insulators and silencers, however are greatly underrepresented in these studies, and no definite histone modification patterns have been described so far. In order to get a full view of the intricate regulation of transcription, it seems vital to improve our understanding of histone modification patterns on all regulatory elements. In this review, an overview of histone modification patterns on regulatory elements, and their importance for transcription regulation is given. Special attention is directed to the patterns on silencers and in silenced genomic regions.