TRIM28 regulates RNA polymerase II promoter-proximal pausing and pause release

Nat Struct Mol Biol. 2014 Oct;21(10):876-83. doi: 10.1038/nsmb.2878. Epub 2014 Aug 31.


Promoter-proximal pausing of RNA polymerase II (Pol II) is a major checkpoint in transcription. An unbiased search for new human proteins that could regulate paused Pol II at the HSPA1B gene identified TRIM28. In vitro analyses indicated HSF1-dependent attenuation of Pol II pausing upon TRIM28 depletion, whereas in vivo data revealed de novo expression of HSPA1B and other known genes regulated by paused Pol II upon TRIM28 knockdown. These results were supported by genome-wide ChIP-sequencing analyses of Pol II occupancy that revealed a global role for TRIM28 in regulating Pol II pausing and pause release. Furthermore, in vivo and in vitro mechanistic studies suggest that transcription-coupled phosphorylation regulates Pol II pause release by TRIM28. Collectively, our findings identify TRIM28 as a new factor that modulates Pol II pausing and transcriptional elongation at a large number of mammalian genes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / antagonists & inhibitors
  • Cell Line, Tumor
  • DNA-Activated Protein Kinase / antagonists & inhibitors
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • HEK293 Cells
  • HSP70 Heat-Shock Proteins / biosynthesis
  • HSP70 Heat-Shock Proteins / genetics*
  • HeLa Cells
  • Heat Shock Transcription Factors
  • Humans
  • Phosphorylation
  • Promoter Regions, Genetic / genetics*
  • RNA Polymerase II / genetics*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription, Genetic / genetics
  • Tripartite Motif-Containing Protein 28


  • DNA-Binding Proteins
  • HSF1 protein, human
  • HSP70 Heat-Shock Proteins
  • HSPA1B protein, human
  • Heat Shock Transcription Factors
  • Repressor Proteins
  • Transcription Factors
  • TRIM28 protein, human
  • Tripartite Motif-Containing Protein 28
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • DNA-Activated Protein Kinase
  • RNA Polymerase II

Associated data

  • GEO/GSE48253