A proline-rich TGF-beta-responsive transcriptional activator interacts with histone H3

Genes Dev. 1995 Dec 15;9(24):3051-66. doi: 10.1101/gad.9.24.3051.

Abstract

The molecular mechanisms involved in the regulation of gene expression by transforming growth factor-beta (TGF-beta) have been analyzed. We show that TGF-beta specifically induces the activity of the proline-rich trans-activation domain of CTF-1, a member of the CTF/NF-I family of transcription factors. A TGF-beta-responsive domain (TRD) in the proline-rich transcriptional activation sequence of CTF-1 was shown to mediate TGF-beta induction in NIH-3T3 cells. Mutagenesis studies indicated that this domain is not the primary target of regulatory phosphorylations, suggesting that the growth factor may regulate a CTF-1-interacting protein. A two-hybrid screening assay identified a nucleosome component, histone H3, as a specific CTF-1-interacting protein in yeast. Furthermore, the CTF-1 trans-activation domain was shown to interact with histone H3 in both transiently and stably transfected mammalian cells. This interaction requires the TRD, and it appears to be upregulated by TGF-beta in vivo. Moreover, point mutations in the TRD that inhibit TGF-beta induction also reduce interaction with histone H3. In vitro, the trans-activation domain of CTF-1 specifically contacts histone H3 and oligomers of histones H3 and H4, and full-length CTF-1 was shown to alter the interaction of reconstituted nucleosomal cores with DNA. Thus, the growth factor-regulated trans-activation domain of CTF-1 can interact with chromatin components through histone H3. These findings suggest that such interactions may regulate chromatin dynamics in response to growth factor signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins*
  • Chromatin / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • Glutamine / metabolism
  • Histones / metabolism*
  • Humans
  • Mice
  • Molecular Sequence Data
  • NFI Transcription Factors
  • Nucleosomes / metabolism
  • Oligodeoxyribonucleotides
  • Point Mutation
  • Proline / metabolism*
  • Promoter Regions, Genetic
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta / metabolism*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CTF-1 transcription factor
  • Chromatin
  • DNA-Binding Proteins
  • Histones
  • NFI Transcription Factors
  • Nucleosomes
  • Oligodeoxyribonucleotides
  • Transcription Factors
  • Transforming Growth Factor beta
  • Glutamine
  • Proline