Epigenetic Genome Editing in Neurological Disorders

Neurological function requires various dynamic changes to regulate a diverse range of cell fate decisions. This process is heavily regulated by epigenetics: heritable changes that do not directly alter the underlying genetic code. Changes to epigenetic layers, such as DNA methylation and histone modification, are tightly controlled by mediators and regulators responding to various physiological and environmental stimuli. Epigenetic dysregulation is associated with complex neurological disorders such as autism, intellectual disability, Alzheimer’s, Huntington's, and Parkinson's disease. Recent advances in gene editing have enabled rapid growth in understanding gene variation and regulatory function in the nervous system, improving previous research lacking necessary genetic and temporal specificity. These tools have further been developed to enable locus-specific epigenetic modification. The rapid development of genome editing tools for altering epigenetic patterns and downstream transcriptional regulation holds promise for the development of potential future targeted epigenetic therapies for many neurological conditions.

The rapidly emerging field of gene editing, and its application to epigenetics, has advanced progress in targeted epigenetic modifications and the modulation of gene expression. This targeted modulation of the epigenome is a powerful tool for researchers in advancing our knowledge of neurological function and disorders.

Epigenetic modifications can be highly dynamic in response to specific brain activity states and experiences such as aging or external stimuli. Various modes of gene regulation interact to coordinate the complex processes of neurological function. Epigenetic regulation, including DNA methylation, histone modifications, non-coding RNAs, and the epitranscriptome, have an emerging role in understanding this process. Epigenetic editing utilizes modified site-specific gene editing techniques coupled with the activity of epigenetic writers and/or erasers. These processes include altering histone markers of gene promoters, enhancers, or specific isoforms.

Multi-omics detection, such as DNA, RNA, methylation, ChIP, and ATAC sequencing, Hi-C, and mass spectrometry, has been used to detect the outcomes of changes in epigenetic regulation by CRISPR, RNAi, ZFN, TALEN, etc. In the field of gene modulation, site-specific epigenetic editing brings a new era of research from understanding the fundamental biological mechanisms to the development of next generation therapies.

For this Research Topic, we welcome the contributions of original research and review articles. Potential topics include, but are not limited to, the following:

• Targeted editing of specific epigenetic modifications.
• Genome-wide modification, including CRISPR screens, multi-targets modifications (such as DNMTs)
• Multi-omics detection: DNA, RNA, methylation, ChIP, ATAC sequencing, Hi-C, and mass spectrometry
• Imaging detection: Microscopy, RNA FISH, smFISH, MERFISH, and in situ detection
• Samples/tissue: cell lines, population studies, brain or other related organs, and human models such as iPSC and cerebral organoids systems relevant to neurological diseases
• Fundamental mechanism research and clinical trails
• Original research and review articles, including discussions of epigenetic gene editing pitfalls and limitations, and future directions of epigenetic gene editing

Keywords: Epigenetics, CRISPR, Gene Editing, Neurological disorders, Multi-Omics

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.