Xu L, Lavinsky R M, Dasen J S, Flynn S E, McInerney E M, Mullen T M, Heinzel T, Szeto D, Korzus E, Kurokawa R, Aggarwal A K, Rose D W, Glass C K, Rosenfeld M G
Howard Hughes Medical Institute, University of California at San Diego, La Jolla 92093-0648, USA.
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.
POU结构域蛋白，如垂体特异性因子Pit-1，是同源结构域蛋白家族的成员，在发育和体内平衡中起重要作用，通过组成性作用或响应信号转导途径来抑制或激活特定基因的表达。我们在此表明，含同源结构域的阻遏物如Rpx2似乎仅募集一种共阻遏物复合物，而Pit-1的活性则由一种含N-CoR/SMRT、mSin3A/B和组蛋白脱乙酰酶的共阻遏物复合物与一种包含CREB结合蛋白（CBP）和p/CAF的共激活物复合物之间的调节平衡所决定。环磷酸腺苷（cAMP）或生长因子对Pit-1的激活分别取决于CBP不同的氨基末端和羧基末端结构域。此外，CBP或p/CAF的组蛋白乙酰转移酶功能分别是cAMP或生长因子刺激的Pit-1功能所必需的。这些数据表明，在介导不同信号转导途径对特定DNA结合转录因子的作用时，对组蛋白乙酰转移酶和CBP结构域的特定需求存在转换。
