Signal-specific co-activator domain requirements for Pit-1 activation

Nature. 1998 Sep 17;395(6699):301-6. doi: 10.1038/26270.


POU-domain proteins, such as the pituitary-specific factor Pit-1, are members of the homeodomain family of proteins which are important in development and homeostasis, acting constitutively or in response to signal-transduction pathways to either repress or activate the expression of specific genes. Here we show that whereas homeodomain-containing repressors such as Rpx2 seem to recruit only a co-repressor complex, the activity of Pit-1 is determined by a regulated balance between a co-repressor complex that contains N-CoR/SMRT, mSin3A/B and histone deacetylases, and a co-activator complex that includes the CREB-binding protein (CBP) and p/CAF. Activation of Pit-1 by cyclic AMP or growth factors depends on distinct amino- and carboxy-terminal domains of CBP, respectively. Furthermore, the histone acetyltransferase functions of CBP or p/CAF are required for Pit-1 function that is stimulated by cyclic AMP or growth factors, respectively. These data show that there is a switch in specific requirements for histone acetyltransferases and CBP domains in mediating the effects of different signal-transduction pathways on specific DNA-bound transcription factors.

Publication types

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

MeSH terms

  • Acetyltransferases / metabolism
  • Binding, Competitive
  • CREB-Binding Protein
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Cyclic AMP / metabolism
  • DNA-Binding Proteins / metabolism*
  • Growth Substances / metabolism
  • HeLa Cells
  • Histone Acetyltransferases
  • Homeodomain Proteins / metabolism*
  • Humans
  • Nuclear Proteins / metabolism
  • Nuclear Receptor Co-Repressor 1
  • Phosphorylation
  • Protein Binding
  • Receptors, Estrogen / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / metabolism
  • Signal Transduction*
  • Trans-Activators / metabolism
  • Transcription Factor Pit-1
  • Transcription Factors / metabolism*
  • p300-CBP Transcription Factors


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Growth Substances
  • Homeodomain Proteins
  • NCOR1 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • POU1F1 protein, human
  • Receptors, Estrogen
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factor Pit-1
  • Transcription Factors
  • Cyclic AMP
  • Acetyltransferases
  • CREB-Binding Protein
  • CREBBP protein, human
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor