A 'molecular switchboard'--covalent modifications to proteins and their impact on transcription.

Proteins undergo a remarkable variety of posttranslational modifications, with more than 200 distinct modifications identified to date. Increasing evidence suggests that many proteins bear multiple, distinct modifications, and the ability of one modification to antagonize or synergize the deposition of another can have significant biological consequences. Here, we illustrate the importance of posttranslational modifications within the context of transcriptional regulation, and we offer a perspective on the emerging role of combinatorial networks of modifications. Finally, we discuss the potential for chemical approaches to transform our understanding of the field.