Subnuclear partitioning and functional regulation of the Pit-1 transcription factor

J Cell Biochem. 1999 Mar 1;72(3):322-38.


Subnuclear compartmentation is postulated to play an important role in many aspects of nuclear metabolism. To directly test an application of this model to transcription factor function, we examined the subnuclear partitioning behavior of Pit-1, a tissue-specific, POU-class transactivator. Biochemical and in situ assays indicate the nuclear pool of Pit-1 is normally divided between two compartments: the majority being differentially soluble in detergent, and a significant insoluble fraction (approximately 20%) bound to the nuclear matrix. Examination of Pit-1 deletion mutants and chimeric fusions reveal the highly conserved 66 amino acid POU-specific domain contains a necessary and sufficient nuclear matrix targeting signal. The nuclear partitioning behavior of several natural or engineered point mutations of Pit-1 was also examined. Surprisingly, the inactive point mutants were completely matrix-bound, irrespective of their ability to bind Pit-1 specific DNA. These results suggest that dynamic partitioning of Pit-1 is a component of its normal transactivator function that takes place upon the insoluble nuclear substructure where transcription occurs.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Blotting, Western
  • Cell Nucleus / chemistry
  • Cell Nucleus / physiology*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Epitopes / chemistry
  • HeLa Cells
  • Humans
  • Immunohistochemistry
  • Nuclear Matrix / chemistry
  • Rats
  • Transcription Factor Pit-1
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transfection


  • Antibodies, Monoclonal
  • DNA-Binding Proteins
  • Epitopes
  • POU1F1 protein, human
  • Pou1f1 protein, rat
  • Transcription Factor Pit-1
  • Transcription Factors