The two-hybrid system is a genetic method that uses transcriptional activity as a measure of protein-protein interaction [1]. It relies on the modular nature of site-specific transcriptional activators, which consist of a DNA-binding domain and a transcriptional activation domain. The DNA-binding domain serves to target the activator to the promoter region of specific genes, and the activation domain contacts other proteins of the transcriptional machinery to enable transcription to occur. The two-hybrid system is based on the observation that the two domains of the activator do not have to be covalently linked and can be brought together by the interaction of any two interacting proteins.
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