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Fig. 1 | Genome Biology

Fig. 1

From: The epigenome: the next substrate for engineering

Fig. 1

Epigenome engineering is the selective manipulation of chromatin and epigenetic modifications in the genome. a Epigenetic modifications provide a rich set of capabilities and challenges for engineering, including 1) a large biochemical diversity, 2) a preponderance of combinatorial interactions, 3) the potential for long-term memory, and 4) the ability to regulate genes over large spatial ranges. b Programmable DNA-binding domains, which have been used extensively in genome engineering applications and are now being harnessed to design epigenome engineering tools. Epigenetic editors are fusions of a DNA-binding module (zinc fingers (ZFs), transcription activator-like effectors (TALEs) or CRISPR-Cas9) to one or more chromatin regulator (CR) modules. Each ZF domain recognizes ~3–4 nucleotide sequences, whereas each TALE domain recognizes a single nucleotide. The Cas9 protein is directed to its target site by an engineered guide RNA (gRNA) that binds genomic sequences via Watson–Crick base pairing. dCas9 nuclease-null Cas9 protein. c The manipulation of chromatin and epigenetic modifications can be understood in terms of reader/writer/eraser schemes. Molecular writers and erasers serve to catalyze the transfer and removal of chemical marks on target histone residues. The mark is then interpreted by readers, which function to recruit and/or alter functionality. Inspired by and adapted from [9]

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