Letters to Nature
Nature 395, 301-306 (17 September 1998) | doi:10.1038/26270; Received 13 March 1998; Accepted 29 June 1998
Signal-specific co-activator domain requirements for Pit-1 activation
Lan Xu1,2, Robert M. Lavinsky1,3, Jeremy S. Dasen1,2, Sarah E. Flynn1, Eileen M. McInerney1, Tina-Marie Mullen1,5,4, Thorsten Heinzel1, Daniel Szeto1,2, Edward Korzus1, Riki Kurokawa5,6, Aneel K. Aggarwal7, David W. Rose4, Christopher K. Glass5,6 & Michael G. Rosenfeld1,6
- Howard Hughes Medical Institute, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0648, USA
- Biomedical Sciences Graduate Program, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0648, USA
- Department of Biology Graduate Program, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0648, USA
- Whittier Diabetes Program, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0648, USA
- Cellular and Molecular Medicine, and University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0648, USA
- Department and School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0648, USA
- Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, New York 10029-6574, USA
Correspondence to: Michael G. Rosenfeld1,6 Correspondence and requests for materials should be addressed to M.G.R. (e-mail: Email: mrosenfeld@ucsd.edu).
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 genes1. Here we show that whereas homeodomain-containing repressors such as Rpx2 seem to recruit only a co-repressor complex, the activity of Pit-1 (ref. 3) is determined by a regulated balance between a co-repressor complex that contains N-CoR/SMRT4,5, mSin3A/B6, 7, 8 and histone deacetylases6, 7, 8 and a co-activator complex that includes the CREB-binding protein (CBP)9 and p/CAF10. Activation of Pit-1 by cyclic AMP or growth factors depends on distinct amino- and carboxy-terminal domains of CBP, respectively. Furthermore, thehistone acetyltransferase functions of CBP11,12 or p/CAF10 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.
