FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH

Mol Cell. 2000 Jun;5(6):1067-72. doi: 10.1016/s1097-2765(00)80272-5.

Abstract

We report that the chromatin-specific transcription elongation factor FACT functions in conjunction with the RNA polymerase II CTD kinase P-TEFb to alleviate transcription inhibition by DSIF (DRB sensitivity-inducing factor) and NELF (negative elongation factor). We find that the kinase activity of TFIIH is dispensable for this activity, demonstrating that TFIIH-mediated CTD phosphorylation is not involved in the regulation of FACT and DSIF/NELF activities. Thus, we propose a novel transcriptional regulatory network in which DSIF/NELF inhibition of transcription is prevented by P-TEFb in cooperation with FACT. This study uncovers a novel role for FACT in the regulation of transcription on naked DNA that is independent of its activities on chromatin templates. In addition, this study reveals functional differences between P-TEFb and TFIIH in the regulation of transcription.

Publication types

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

MeSH terms

  • DNA-Binding Proteins*
  • Drosophila Proteins*
  • Gene Expression Regulation
  • High Mobility Group Proteins*
  • Humans
  • Mutation
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Positive Transcriptional Elongation Factor B
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism
  • Repressor Proteins*
  • Transcription Factor TFIIH
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors, TFII*
  • Transcription, Genetic*
  • Transcriptional Elongation Factors*

Substances

  • DNA-Binding Proteins
  • DSIF protein, Drosophila
  • Drosophila Proteins
  • High Mobility Group Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • SSRP protein, Drosophila
  • SSRP1 protein, human
  • SUPT4H1 protein, human
  • SUPT5H protein, human
  • Transcription Factors
  • Transcription Factors, TFII
  • Transcriptional Elongation Factors
  • negative elongation factor
  • Transcription Factor TFIIH
  • Positive Transcriptional Elongation Factor B
  • Protein-Serine-Threonine Kinases
  • RNA Polymerase II