ABSTRACT Development of an organism depends on differential expression/regulation of genes in the genome to produce diverse cell types during the developmental processes. A typical animal/plant genome contains a certain/fixed number of genes, all of these are not expressed all the times. Depending on the differential expression of the genes under varying environmental conditions, the morphology/physiology of the organism may vary. Epigenetic variations (DNA and histone modifications, and variation in small-RNA biogenesis) play important roles in the regulation of gene expression during the developmental process and environmental stresses. Genome editing helps unravelling the function(s) of a gene, and editing/correcting the gene of interest. Once we identify the epigenetic mark(s) associated with the trait of interest, we can use epigenome editing tools and techniques for manipulation of gene expression. Epigenome editing uses a fusion protein comprising a specific DNA recognition domain that recruits the attached enzymatic domain to the defined genomic site. Discovery of dCas9 provides a valuable tool for epigenome editing. However, gene expression is regulated depending on the dynamic and reversibly modifiable biological and chemical information in the epigenome/epitranscriptome. Recruitment of dCas9 fused with histone-acetyltransferase or Tet1 DNA-demethylase can be used to activate enhancers and thus gene expression. Even reversible recruitment of endogenous chromatin complexes to a genomic locus is possible in almost any cell type. Deploying heterochromatin complex (e.g. Hp1/Suv39h1) and chromatin-remodelling complex (e.g. BAF), there are possibilities of repression or activation of genes through epigenome. The recent developments with respect to base- and prime-editing promise to add precision in epigenome and epitranscriptome editing, respectively. This review provides newer insights into fine-tuning of gene expression through genome/epigenome editing, and thus might help unravelling some of the enigmas of developmental biology.
View Full Article
|