Fang Xiangdong, Han Hemei, Stamatoyannopoulos George, Li Qiliang
Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA.
J Biol Chem. 2004 Feb 13;279(7):5444-9. doi: 10.1074/jbc.M306241200. Epub 2003 Nov 26.
The CCAAT box is a widespread motif in eukaryotic promoters. In this study we demonstrate that the effects of the CCAAT box on gamma-globin gene activation are developmentally distinct. Although this promoter element is essential for high level gamma gene expression in adult erythropoiesis, it plays little role in embryonic erythroid cells. The CCAAT mutation in the human gamma-globin gene promoter impairs recruitment of TATA-binding protein (TBP), TFIIB, and RNA polymerase II in adult splenic erythroblasts but not in embryonic erythroid cells. We also show that the efficiency of gamma gene transcription is correlated with recruitment of TBP on the TATA box but that the level of TBP recruitment is not nuclear factor Y (NF-Y)-dependent. Our data also suggest that it is unlikely that transcriptional stimulation by the CCAAT box is exerted through direct protein-protein interaction between NF-Y and TBP.
CCAAT框是真核生物启动子中广泛存在的基序。在本研究中，我们证明CCAAT框对γ-珠蛋白基因激活的影响在发育过程中是不同的。尽管该启动子元件对于成人红细胞生成中高水平的γ基因表达至关重要，但它在胚胎红细胞中作用很小。人类γ-珠蛋白基因启动子中的CCAAT突变会损害成人脾脏成红细胞中TATA结合蛋白（TBP）、TFIIB和RNA聚合酶II的募集，但在胚胎红细胞中则不会。我们还表明，γ基因转录效率与TBP在TATA框上的募集相关，但TBP募集水平不依赖于核因子Y（NF-Y）。我们的数据还表明，CCAAT框的转录刺激不太可能通过NF-Y和TBP之间的直接蛋白质-蛋白质相互作用来实现。
