Abstract
Proper regulation of the chromatin landscape is essential for maintaining eukaryotic cell identity and diverse cellular processes. The importance of the epigenome comes, in part, from the ability to influence gene expression through patterns in DNA methylation, histone tail modification, and chromatin architecture. Decades of research have associated this process of chromatin regulation and gene expression with human diseased states. With the goal of understanding how chromatin dysregulation contributes to disease, as well as preventing or reversing this type of dysregulation, a multidisciplinary effort has been launched to control the epigenome. Chemicals that alter the epigenome have been used in labs and in clinics since the 1970s, but more recently there has been a shift in this effort towards manipulating the chromatin landscape in a locus-specific manner. This review will provide an overview of chromatin biology to set the stage for the type of control being discussed, evaluate the recent technological advances made in controlling specific regions of chromatin, and consider the translational applications of these works.
Highlights
Differential regulation of the chromatin landscape allows for genetically identical eukaryotic cells to perform specific, discrete functions [1]
Models that describe the close interplay between specific chromatin environments and their associated transcriptional activities are based on two characteristics: the physical accessibility of the DNA due to the level of chromatin compaction and the recruitment of transcriptional machinery by chromatin modifications
Development of new ways to tether proteins and proteins associated with RNA to chromatin has opened up the ability to modulate specific endogenous genes by an assortment of chromatin modifying activities
Summary
Differential regulation of the chromatin landscape (composed of DNA wrapped around histone linkers or octamers) allows for genetically identical eukaryotic cells to perform specific, discrete functions [1]. Chromatin compaction has been identified as a physical determinant of DNA’s accessibility to transcription-initiating proteins, and these processes are highly regulated through deposition of histone protein variants, ATP-dependent nucleosome remodeling, methylation of DNA, and posttranslational modifications of histone tails [5]. These interrelated processes work in concert to control transcriptional activity, DNA replication, damage repair, and nuclear organization [4,6,7,8]. Two of the most widely studied nucleotide modifications are methylation (of DNA and of the lysine residue) and acetylation (of the lysine residue) [17] These chromatin-based mechanisms are commonly used in the field of epigenetic biotechnology to control gene expression. The classification and function of the proteins mediating DNA methylation and lysine methylation/acetylation are important for the design of chromatin recruitment tools
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