Possible Targets for Heterochromatin to Euchromatin Transition of Genes Using CRISPR/dCas9-Mediated Epigenome Editing

Among different epigenetic mechanisms affecting transcription, lots of efforts have been made to alter the state of DNA methylation and also activation/repression of gene expression through targeting cis-regulatory elements using nuclease deficient Cas9 (dCas9). Although chromatin modification by CRISPR/Cas9 technology allocates a significant part of researches in the field of epigenome editing, researchers have focused only on deactivation of genes by changing the locus state of genes from euchromatin to heterochromatin (1). Heterochromatin/euchromatin status of chromosome is dynamic and Environmental factors may lead to transition of loci state from euchromatin to heterochromatin and somehow this change may remain through the rest of cell life. Heterochromatin protein HP1a and histone H3K9 methyltransferase are the key elements in position-effect variegation (PEV) and heterochromatin formation and as a result, juxtaposed genes of euchromatin with heterochromatin (2). Histone methylation is not irreversible and several histone demethylases are expressed in cells. HP1a contributes not only in gene silencing but also in activation of genes. This protein can bind to different proteins such as histone methyl-transferases and demethylases and since the effect of histone methylation on gene expression depends on the position of methylated lysine(3), engineering the methylation status of adjacent histones to a specific gene by CRISPR/dCas9 would be a promising idea. In this review, I want to study the feasibility of using HP1 and various histone methyl-transferases and demethylases for CRISPR/dCas9-mediated epigenome editing and discuss the advantages and possible obstacles.

References:

• Pulecio, J, et al., 2017. CRISPR/Cas9-based engineering of the epigenome. Cell Stem Cell, 21(4), pp.431-447.
• Elgin, S.C. and Reuter, G., 2013. Position-effect variegation, heterochromatin formation, and gene silencing in Drosophila. Cold Spring Harbor perspectives in biology, 5(8), p.a017780.
• Kwon, S.H. and Workman, J.L., 2011. The changing faces of HP1: from heterochromatin formation and gene silencing to euchromatic gene expression. Bioessays, 33(4), pp.280-289.