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TALEored Epigenetics: A DNA‐Binding Scaffold for Programmable Epigenome Editing and Analysis

Epigenetic modification of the cytosine 5‐position is an important regulator of gene expression with essential roles in genome stability, development, and disease. In addition to 5‐methylcytosine (mC), the oxidized mC derivatives 5‐hydroxymethyl‐, 5‐formyl‐, and 5‐carboxylcytosine (hmC, fC, and caC) have recently been discovered. These are intermediates of an active demethylation pathway but might also represent new epigenetic marks with individual biological roles. This increase in chemical complexity of DNA‐encoded information has created a pressing need for new approaches that allow reading and editing of this information. Transcription‐activator‐like effectors (TALEs) are DNA‐binding domains with programmable sequence selectivity that enable the direct reading of epigenetic cytosine modifications but can also guide enzymatic editing domains to genomic loci of choice. Here, we review recent advances in employing TALEs for these applications.