Functional interaction between the POU domain protein Tst-1/Oct-6 and the high-mobility-group protein HMG-I/Y

Mol Cell Biol. 1995 Jul;15(7):3738-47. doi: 10.1128/MCB.15.7.3738.

Abstract

The POU domain protein Tst-1/Oct-6 is a transcriptional activator of human papovavirus JC virus in transient transfections. Because of its endogenous expression in myelinating glia, Tst-1/Oct-6 might also be an important determinant for the glia specificity of JC virus in vivo. Activation of viral early and late genes depends on the ability of Tst-1/Oct-6 to interact with an AT-rich element within the viral regulatory region. Here, we show that this element not only is bound by Tst-1/Oct-6 but, in addition, serves as a binding site for the high-mobility-group protein HMG-I/Y. In the presence of HMG-I/Y, Tst-1/Oct-6 exhibited an increased affinity for this AT-rich element. The specificity of this effect was evident from the fact that no stimulation of Tst-1/Oct-6 binding was observed on a site that did not allow binding of HMG-I/Y. In addition, both proteins interacted with each other in solution. Direct contacts were identified between the POU domain of Tst-1/Oct-6 and a short stretch of 10 amino acids in the central portion of HMG-I/Y. These results point to an accessory role for HMG-I/Y in the activation of JC viral gene expression by the POU domain protein Tst-1/Oct-6. In agreement with such a role, HMG-Y synergistically supported the function of Tst-1/Oct-6 in transient transfections, measured on the early promoter of JC virus or on an artificial promoter consisting of only a TATA box and the common binding element for Tst-1 and HMG-I/Y.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromatin / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Viral
  • Genes, Reporter
  • Glioblastoma
  • HMGA1a Protein
  • High Mobility Group Proteins / metabolism*
  • Humans
  • JC Virus / genetics*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuroglia / virology
  • Octamer Transcription Factor-6
  • POU Domain Factors
  • Promoter Regions, Genetic*
  • Protein Binding
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Chromatin
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Nerve Tissue Proteins
  • POU Domain Factors
  • POU3F1 protein, human
  • Transcription Factors
  • HMGA1a Protein
  • Octamer Transcription Factor-6