RNA polymerase II transcription initiation with and without XPB translocase activity

A key step in gene expression is the opening of DNA at the transcription start site (TSS), allowing RNA polymerase to begin RNA synthesis. In eukaryotes, RNA polymerase II initiates transcription within the pre-initiation complex (PIC), which includes TFIIH. The XPB subunit of TFIIH drives DNA unwinding at the TSS through ATP-dependent activity. However, some promoters enable transcription without XPB, likely due to intrinsically unstable DNA that does not require active unwinding. This mechanism may reflect an evolutionary remnant of archaeal transcription. This perspective suggests that transcription initiation at certain human promoters does not require the translocase activity of the XPB subunit of TFIIH, as their intrinsic thermodynamic instability enables DNA opening without active unwinding.