Q-rich activation domains: flexible 'rulers' for transcription start site selection?

Recent findings broadened the function of RNA polymerase II (Pol II) proximal promoter motifs from quantitative regulators of transcription to important determinants of transcription start site (TSS) position. These motifs are recognized by transcription factors (TFs) that we propose to term ‘ruler’ TFs (rTFs), such as NRF1, NF-Y, YY1, ZNF143, BANP, and members of the SP, ETS, and CRE families, sharing as a common feature a glutamine-rich (Q-rich) effector domain also enriched in valine, isoleucine, and threonine (QVIT-rich). We propose that rTFs guide TSS location by constraining the position of the pre-initiation complex (PIC) during its promoter recognition phase through a specialized, and still enigmatic, class of activation domains.