RNA Polymerase II transcription independent of TBP in murine embryonic stem cells

Elife. 2023 Mar 30;12:e83810. doi: 10.7554/eLife.83810.


Transcription by RNA Polymerase II (Pol II) is initiated by the hierarchical assembly of the pre-initiation complex onto promoter DNA. Decades of research have shown that the TATA-box binding protein (TBP) is essential for Pol II loading and initiation. Here, we report instead that acute depletion of TBP in mouse embryonic stem cells has no global effect on ongoing Pol II transcription. In contrast, acute TBP depletion severely impairs RNA Polymerase III initiation. Furthermore, Pol II transcriptional induction occurs normally upon TBP depletion. This TBP-independent transcription mechanism is not due to a functional redundancy with the TBP paralog TRF2, though TRF2 also binds to promoters of transcribed genes. Rather, we show that the TFIID complex can form and, despite having reduced TAF4 and TFIIA binding when TBP is depleted, the Pol II machinery is sufficiently robust in sustaining TBP-independent transcription.

Keywords: chromosomes; degron; embryonic stem cells; gene expression; genomics; mouse; transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism
  • Embryonic Stem Cells / metabolism
  • Mice
  • RNA Polymerase II* / metabolism
  • RNA Polymerase III / genetics
  • TATA Box / genetics
  • TATA-Box Binding Protein / genetics
  • TATA-Box Binding Protein / metabolism
  • Transcription Factor TFIID / genetics
  • Transcription Factor TFIID / metabolism
  • Transcription Factors* / metabolism
  • Transcription, Genetic


  • Transcription Factors
  • RNA Polymerase II
  • DNA-Binding Proteins
  • TATA-Box Binding Protein
  • Transcription Factor TFIID
  • RNA Polymerase III

Associated data

  • GEO/GSE172401