Mutations affecting transcription factor function. (A) TFs and bound cofactors (Cofs) regulate gene expression by binding cognate cis elements within DNA regulatory regions including promoters or enhancers (gray box). The arrow indicates gene transcription. (B) Mutations in the TF DNA binding domain inhibit TF interactions with some or all cis elements. The dashed lines indicate altered transcription. (C) TF mutations that inhibit Cof binding alter gene expression at some or all target genes. (D) Some Cof interactions are required for in vivo DNA occupancy by TFs. Thus, TF mutations outside of the DNA binding domain can inhibit gene occupancy. (E) Mutations in DNA cis elements can impair TF occupancy at a single site within one gene, thereby altering its transcription.