Emerging Molecular Targets for Brain Repair after Stroke

Figure 1

There are three main epigenetic mechanisms. (1) The first includes the mechanisms mediating DNA methylation, typically at cytosine residues in gene promoter regions. These reactions attenuate gene expression and are catalyzed by multiple different isoforms of DNA methyltransferases. An important requirement for these reactions is a methyl donor, typically folic acid supplied through the diet. (2) The second epigenetic category of mechanisms includes the enzymes that acetylate and deacetylate lysine residues on histone proteins. These enzymes regulate chromatin structure and include histone acetyltransferases and histone deacetylases. In general, histone acetylation promotes dissociation from DNA and facilitates gene expression, whereas deacetylation promotes reassociation and reduced gene expression. (3) The third epigenetic category includes the pathways that transcribe, process, and transport microRNA, endogenous short interfering RNAs (siRNAs), and exogenous siRNAs. Endogenous microRNAs are transcribed from nuclear genes into primary microRNA transcripts, which are cleaved into precursor microRNA transcripts. The nuclear protein, Exportin 5, transports precursor microRNAs onto the cytoplasm, where it is cleaved by Dicer to an imperfect miR-X : miR-X* duplex. One strand of the duplex is degraded and the remaining, mature microRNA binds Dicer and Argonaute (Ago) proteins to form RNA-induced silencing complexes (RISCs). MicroRNAs target sequences within cellular mRNAs. Parallel processes in the cytoplasm produce siRNAs derived from endogenous transposons, or from exogenous siRNAs and target cellular or viral mRNAs.