Reconstitution of recombinant TFIIH that can mediate activator-dependent transcription

Genes Cells. 2001 Aug;6(8):707-19. doi: 10.1046/j.1365-2443.2001.00456.x.

Abstract

Background: TFIIH is one of the general transcription factors required for accurate transcription of protein-coding genes by RNA polymerase II. TFIIH has helicase and kinase activities, plays a role in promoter opening and promoter escape, and is also implicated in efficient activator-dependent transcription.

Results: We have established a reconstitution system of recombinant TFIIH using a three-virus baculovirus expression system. The recombinant TFIIH was active in CTD kinase and DNA helicase assays, and showed both basal and activator-dependent transcriptional activities that were indistinguishable from those of HeLa cell-derived TFIIH. Further analyses using recombinant TFIIH confirmed a critical role of TFIIH in activator-dependent transcription. The dose response of TFIIH in activator-dependent transcription suggested that mere recruitment of TFIIH is not sufficient for transcriptional activation. The sensitivity of activator-dependent transcription to nonhydrolysable ATP analogues indicated the importance of the enzymatic activities of TFIIH in transcriptional activation.

Conclusions: Our results raise a possibility that transcriptional activation by GAL4-VP16 requires enzymatic activities. Recombinant TFIIH reconstituted from this baculovirus system should be useful for analysis of the mechanisms of activation by GAL4-VP16.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Baculoviridae
  • Cloning, Molecular / methods
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Hydrolysis
  • Promoter Regions, Genetic
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • RNA Polymerase II / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Trans-Activators / metabolism
  • Transcription Factor TFIIH
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • Transcription Factors, TFII*
  • Transcription, Genetic*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • DNA-Binding Proteins
  • Gal-VP16
  • Recombinant Proteins
  • Trans-Activators
  • Transcription Factors
  • Transcription Factors, TFII
  • Transcription Factor TFIIH
  • Adenosine Triphosphate
  • Protein Serine-Threonine Kinases
  • RNA Polymerase II
  • DNA Helicases