Scully K M, Jacobson E M, Jepsen K, Lunyak V, Viadiu H, Carrière C, Rose D W, Hooshmand F, Aggarwal A K, Rosenfeld M G
Howard Hughes Medical Institute, Department of Endocrinology and Metabolism, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Science. 2000 Nov 10;290(5494):1127-31. doi: 10.1126/science.290.5494.1127.
Reciprocal gene activation and restriction during cell type differentiation from a common lineage is a hallmark of mammalian organogenesis. A key question, then, is whether a critical transcriptional activator of cell type-specific gene targets can also restrict expression of the same genes in other cell types. Here, we show that whereas the pituitary-specific POU domain factor Pit-1 activates growth hormone gene expression in one cell type, the somatotrope, it restricts its expression from a second cell type, the lactotrope. This distinction depends on a two-base pair spacing in accommodation of the bipartite POU domains on a conserved growth hormone promoter site. The allosteric effect on Pit-1, in combination with other DNA binding factors, results in the recruitment of a corepressor complex, including nuclear receptor corepressor N-CoR, which, unexpectedly, is required for active long-term repression of the growth hormone gene in lactotropes.
在从共同谱系进行细胞类型分化过程中的相互基因激活和限制是哺乳动物器官发生的一个标志。那么，一个关键问题是，细胞类型特异性基因靶点的关键转录激活因子是否也能限制同一基因在其他细胞类型中的表达。在这里，我们表明，垂体特异性POU结构域因子Pit-1在一种细胞类型即生长激素细胞中激活生长激素基因表达，而在第二种细胞类型即催乳激素细胞中则限制其表达。这种差异取决于在保守的生长激素启动子位点上容纳二分体POU结构域时的两个碱基对间距。对Pit-1的变构效应与其他DNA结合因子相结合，导致募集一个共抑制复合物，包括核受体共抑制因子N-CoR，出乎意料的是，这是催乳激素细胞中生长激素基因长期有效抑制所必需的。
