Editing the epigenome: technologies for programmable transcription and epigenetic modulation

Gene regulation is a highly complex and tightly controlled process that defines cell identity, health, and response to environmental signals. Technologies for precisely perturbing gene regulation are critical for improving our understanding of its coordination and for manipulating pathways for applications in biotechnology and medicine. Recently developed DNA-targeting platforms, including zinc finger proteins, TALEs, and CRISPR/Cas9, have enabled the recruitment of transcriptional modulators and epigenome-modifying factors to any genomic site. These technologies are generating novel insights into the function of epigenetic marks and the role of genome structure in gene expression. Additionally, custom transcriptional and epigenetic regulation is facilitating refined control over cell function and decision-making. The unique properties of the CRISPR/Cas9 system have also created new opportunities for multiplexing targets and manipulating complex gene expression patterns, as well as high-throughput genetic screens. This review summarizes recent technology developments in this area and their applications to modern biomedical challenges. We also discuss remaining limitations and necessary future directions for this field.