The ts13 mutation in the TAF(II)250 subunit (CCG1) of TFIID directly affects transcription of D-type cyclin genes in cells arrested in G1 at the nonpermissive temperature

Mol Cell Biol. 1997 Jun;17(6):3284-94. doi: 10.1128/MCB.17.6.3284.

Abstract

The general transcription initiation factor TFIID contains the TATA-binding protein (TBP) and TBP-associated factors (TAFs) implicated in the function of gene-specific activators. Previous studies have indicated that a hamster cell line (ts13) with a point mutation in the TAF(II)250/CCG1 (TAF(II)250) gene shows temperature-sensitive expression of a subset of genes and arrests in late G1 at 39.5 degrees C. Here, we report the identification of cell cycle-specific (G1-specific) genes that appear to be regulated directly through TAF(II)250 both in vivo and in vitro. Transcription rates of several cell cycle-regulatory genes were determined by run-on assays in nuclei from ts13 cells grown at permissive (33 degrees C) and nonpermissive (39.5 degrees C) temperatures. Temperature-dependent differences in transcription rates were observed for cyclin A, D1, and D3 genes. In transient-transfection assays, the human cyclin D1 promoter fused to a luciferase reporter showed a temperature-dependent reduction in activity in ts13 cells but not in parental BHK cells. In in vitro assays, upstream sequence-dependent transcription from the human cyclin D1 promoter was significantly reduced in ts13 nuclear extracts preincubated at 30 degrees C but not in similarly treated BHK nuclear extracts, and transcription in the ts13 extract was restored by addition of an affinity-purified human TFIID. Preincubation of the ts13 nuclear extracts did not affect the function of several GAL4-activation domain fusion proteins (GAL4-VP16, GAL4-p65, and GAL4-p53) on either the adenovirus major late or cyclin D1 core promoter bearing GAL4 sites, further indicating that the effect of the TAF(II)250 mutation is both core promoter and activator specific.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • Cyclin D
  • Cyclin D1
  • Cyclin D3
  • Cyclins / genetics*
  • DNA-Binding Proteins / genetics*
  • G1 Phase*
  • Histone Acetyltransferases
  • Humans
  • Mesocricetus
  • Mutagenesis
  • Nuclear Proteins / genetics*
  • Oncogene Proteins / genetics
  • Promoter Regions, Genetic
  • TATA Box / genetics*
  • TATA-Binding Protein Associated Factors*
  • Temperature
  • Trans-Activators / genetics*
  • Transcription Factor TFIID
  • Transcription Factors, TFII / genetics*
  • Transcription, Genetic*

Substances

  • CCND3 protein, human
  • Cyclin D
  • Cyclin D3
  • Cyclins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Oncogene Proteins
  • TATA-Binding Protein Associated Factors
  • Trans-Activators
  • Transcription Factor TFIID
  • Transcription Factors, TFII
  • Cyclin D1
  • Histone Acetyltransferases
  • TATA-binding protein associated factor 250 kDa