Survey of variation in human transcription factors reveals prevalent DNA binding changes

Variation and transcription factor binding Little is known about the phenotypic and functional effects of genetic variants that result in amino acid changes within functional proteins. Barrera et al. investigated whether amino acid variants changed the DNA binding specificity or affinity of transcription factors. Predictive analyses identified changes in the proteins, and protein-binding microarrays verified changes that affected transcription factor function, including those associated with disease. Thus, within-human protein sequence variation can affect transcriptional regulatory networks, which, depending on the genetic variant, may confer robustness and buffer against amino acid changes and could explain phenotypic variation among individuals. Science , this issue p. 1450