Regulation of Gene Expression and the Elucidative Role of CRISPR-Based Epigenetic Modifiers and CRISPR-Induced Chromosome Conformational Changes

In complex multicellular systems, gene expression is regulated at multiple stages through interconnected complex molecular pathways and regulatory networks. Transcription is the first step in gene expression and is subject to multiple layers of regulation in which epigenetic mechanisms such as DNA methylation, histone tail modifications, and chromosomal conformation play an essential role. In recent years, CRISPR-Cas9 systems have been employed to unearth this complexity and provide new insights on the contribution of chromatin dysregulation in the development of genetic diseases, as well as new tools to prevent or reverse this dysregulation. In this review, we outline the recent development of a variety of CRISPR-based epigenetic editors for targeted DNA methylation/demethylation, histone modification, and three-dimensional DNA conformational change, highlighting their relative performance and impact on gene regulation. Finally, we provide insights on the future developments aimed to accelerate our understanding of the causal relationship between epigenetic marks, genome organization, and gene regulation.

Automated summary

Gene expression in complex multicellular systems is regulated at multiple stages through transcription and epigenetic mechanisms. The use of CRISPR-Cas9 systems has provided new insights into chromatin dysregulation in genetic diseases, as well as tools for targeted DNA modifications. Future developments are focused on understanding the causal relationship between epigenetic marks, genome organization, and gene regulation.