Next-generation sequencing and epigenomics research: a hammer in search of nails

Abstract

After the initial enthusiasm of the human genome project, it became clear that without additional data pertaining to the epigenome, i.e., how the genome is marked at specific developmental periods, in different tissues, as well as across individuals and species-the promise of the genome sequencing project in understanding biology cannot be fulfilled. This realization prompted several large-scale efforts to map the epigenome, most notably the Encyclopedia of DNA Elements (ENCODE) project. While there is essentially a single genome in an individual, there are hundreds of epigenomes, corresponding to various types of epigenomic marks at different developmental times and in multiple tissue types. Unprecedented advances in next-generation sequencing (NGS) technologies, by virtue of low cost and high speeds that continue to improve at a rate beyond what is anticipated by Moore's law for computer hardware technologies, have revolutionized molecular biology and genetics research, and have in turn prompted innovative ways to reduce the problem of measuring cellular events involving DNA or RNA into a sequencing problem. In this article, we provide a brief overview of the epigenome, the various types of epigenomic data afforded by NGS, and some of the novel discoveries yielded by the epigenomics projects. We also provide ample references for the reader to get in-depth information on these topics.

Keywords: chromatin accessibility; epigenomics; methylation; next-generation sequencing; regulation.

Fig. 1

A schematic depicting the context of several epigenetic marks on chromatin; ranging from DNA methylation, nucleosome positioning patterns affecting the size and distribution of DNase I hypersensitive sites, transcriptional activity at non-coding sites leading to the production of small and long RNA, chemical modifications of histone moieties (e.g., mono-, di- and tri-methylation of the 4th lysine of the H3 subunit), and chromatin folding to form localized structures in 3D nuclear space (anticlockwise). Adapted from Fig. 1 in Telese et al. [9], Copyright©2013, with permission from Elsevier.