Genome engineering technologies based on synthetic nucleases and transcription factors enable the targeted modification of the sequence and expression of genes. These engineered nucleases and transcription factors typically consist of a DNA-binding domain linked to an effector module. Zinc finger proteins (ZFPs) and transcription activator-like effector (TALE) DNA-binding domains were discovered in nature and systems have been developed to engineer synthetic versions of these proteins with the potential to recognize any nucleotide sequence in the genome. Genomic engineering is the synthetic assembly of complete chromosomal DNA that is more or less derived from natural genomic sequences. Genomic engineering is the top-down, global approach to synthetic biology; to be distinguished from bottom-up, local genetic circuit engineering.