SIGNAL-SPECIFIC COACTIVATOR DOMAIN REQUIREMENTS FOR PIT-1 ACTIVATION

POU-domain proteins, such as the pituitary-specific factor Pit-1, are members of the homeodomain family of proteins which are important in d evelopment and homeostasis, acting constitutively or in response to si gnal-transduction pathways to either repress or activate the expressio n of specific genes(1). Here we show that whereas homeodomain-containi ng repressors such as Rpx(2) seem to recruit only a co-repressor compl ex, the activity of Pit-1 (ref. 3) is determined by a regulated balanc e between a co-repressor complex that contains N-CoR/SMRT4,5, mSin3A/B 6-8 and histone deacetylases(6-8), and a co-activator complex that inc ludes the CREB-binding protein (CBP)(9) and p/CAF(10). Activation of P it-1 by cyclic AMP or growth factors depends on distinct amino- and ca rboxy-terminal domains of CBP, respectively. Furthermore, the histone acetyltransferase functions of CBP11,12 or p/CAF(10) are required for Pit-1 function that is stimulated by cyclic AMP or growth factors, res pectively. These data show that there is a switch in specific requirem ents for histone acetyltransferases and CBP domains in mediating the e ffects of different signal-transduction pathways on specific DNA-bound transcription factors.