RT Journal Article SR Electronic T1 A TBP-independent mechanism for RNA Polymerase II transcription JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.28.437425 DO 10.1101/2021.03.28.437425 A1 Kwan, James Z.J. A1 Nguyen, Thomas F. A1 BudzyƄski, Marek A. A1 Cui, Jieying A1 Price, Rachel M. A1 Teves, Sheila S. YR 2021 UL http://biorxiv.org/content/early/2021/03/29/2021.03.28.437425.abstract AB Transcription by RNA Polymerase II (Pol II) is initiated by the hierarchical assembly of the Pre-Initiation Complex onto promoter DNA. Decades of in vitro and yeast research have shown that the TATA-box binding protein (TBP) is essential to Pol II initiation by triggering the binding of other general transcription factors, and ensuring proper Pol II loading. Here, we report instead that acute depletion of TBP in mouse embryonic stem cells (mESCs) has no global effect on ongoing Pol II transcription. Surprisingly, Pol II transcriptional induction through the Heat Shock Response or cellular differentiation also occurs normally in the absence of TBP. In contrast, acute TBP depletion severely impairs initiation by RNA Polymerase III. Lastly, we show that a metazoan-specific paralog of TBP is expressed in mESCs and that it binds to promoter regions of active Pol II genes even in the absence of TBP. Taken together, our findings reveal an unexplored TBP-independent process in mESCs that points to a diversity in Pol II transcription initiation mechanisms.Competing Interest StatementThe authors have declared no competing interest.