TBP facilitates RNA Polymerase I transcription following mitosis

Abstract

The TATA-box binding protein (TBP) is the sole transcription factor common in the initiation complexes of the three major eukaryotic RNA Polymerases (Pol I, II, and III). Decades of research have shown that TBP is essential for proper transcription by the three RNA Pols, though the emergence of TBP paralogs throughout evolution have expanded the complexity in RNA Pol initiation. We have previously shown that acute TBP depletion in mouse embryonic stem cells led to a global decrease in Pol III activity, consistent with the requirement of TBP in Pol III initiation. In contrast, Pol II transcription remained unaffected in the absence of TBP and its paralogs. In this report, we show that, in contrast to Pol II-transcribed genes, the TBP paralog TRF2 does not bind to Pol I promoters, and therefore cannot functionally replace TBP upon depletion. Importantly, acute TBP depletion has no major effect on Pol I occupancy or activity on ribosomal RNA genes, but TBP binding in mitosis leads to efficient Pol I reactivation following cell division. These findings provide a more nuanced role for TBP in Pol I transcription in murine embryonic stem cells.