Qi Yingchuan, Ranish Jeffrey A, Zhu Xiaoyan, Krones Anna, Zhang Jie, Aebersold Ruedi, Rose David W, Rosenfeld Michael G, Carrière Catherine
Howard Hughes Medical Institute and Department of Medicine, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2481-6. doi: 10.1073/pnas.0712196105. Epub 2008 Feb 13.
Enhancers have been functionally described for >35 years, but the molecular principles underlying the integration of regulatory inputs to alternate gene enhancers used during mammalian organogenesis remain incompletely understood. Using a combination of in vivo enhancer mapping and proteomics approaches, we have established that two distant and distinct early enhancers, each requiring different transcription complexes, are required for full activation of the gene encoding the pituitary lineage determining factor, Pit1. A transcription factor belonging to the "giant, multiple-homeodomain and zinc finger family," Atbf1, serves as a novel pituitary regulator for one of the two required enhancers as shown by genetic and in vitro analysis.
增强子在功能上已被描述了35年以上，但在哺乳动物器官发生过程中，调控输入整合到交替基因增强子的分子原理仍未完全了解。通过结合体内增强子图谱绘制和蛋白质组学方法，我们确定了两个遥远且不同的早期增强子，每个增强子都需要不同的转录复合物，它们是垂体谱系决定因子Pit1编码基因完全激活所必需的。遗传和体外分析表明，属于“巨大的、多个同源结构域和锌指家族”的转录因子Atbf1是两个必需增强子之一的新型垂体调节因子。
