Comprehensive analysis of epigenetic signatures of human transcription control

Mol Omics. 2021 Oct 11;17(5):692-705. doi: 10.1039/d0mo00130a.


Advances in sequencing technologies have enabled exploration of epigenetic and transcriptional profiles at a genome-wide level. The epigenetic and transcriptional landscapes are now available in hundreds of mammalian cell and tissue contexts. Many studies have performed multi-omics analyses using these datasets to enhance our understanding of relationships between epigenetic modifications and transcription regulation. Nevertheless, most studies so far have focused on the promoters/enhancers and transcription start sites, and other features of transcription control including exons, introns and transcription termination remain underexplored. We investigated the interplay between epigenetic modifications and diverse transcription features using the data generated by the Roadmap Epigenomics project. A comprehensive analysis of histone modifications, DNA methylation, and RNA-seq data of thirty-three human cell lines and tissue types allowed us to confirm the generality of previously described relationships, as well as to generate new hypotheses about the interplay between epigenetic modifications and transcription features. Importantly, our analysis included previously under-explored features of transcription control, namely, transcription termination sites, exon-intron boundaries, and the exon inclusion ratio. We have made the analyses freely available to the scientific community at for easy exploration, validation and hypothesis generation.