Transcription factors regulate gene expression by binding specific sequences on DNA, which is an essential step to produce messenger RNAs from protein-coding genes. Denes Hnisz’s lab, in collaboration with Martin Vingron’s lab at the MPIMG, has discovered that human transcription factors don’t typically use their full potential. Instead, important protein regions within transcription factors encode chemical features that generate submaximal transcriptional activity. The findings, published in Nature Cell Biology, suggest simple ways to engineer natural transcription factor variants with elevated or “optimized” activity, with potential applications for regenerative therapy.