A post-translational modification code for transcription factors: sorting through a sea of signals

Cellular responses to environmental or physiological cues rely on transduction pathways that must ensure discrimination between different signals. These cascades ‘crosstalk’ and lead to a combinatorial regulation. This often results in different combinations of post-translational modifications (PTMs) on target proteins, which might act as a molecular barcode. Although appealing, the idea of the existence of such a code for transcription factors is debated. Using general arguments and recent evidence, we propose that a PTM code is not only possible but necessary in the context of transcription factors regulating multiple processes. Thus, the coding potential of PTM combinations should both provide a further layer of information integration from several transduction pathways and warrant highly specific cellular outputs.