Synergistic transactivation of the differentiation-dependent lung gene Clara cell secretory protein (secretoglobin 1a1) by the basic region leucine zipper factor CCAAT/enhancer-binding protein A and the homeodomain factor Nkx2.1/thyroid transcription factor-1
Synergistic transactivation of the differentiation-dependent lung gene Clara cell secretory protein (secretoglobin 1a1) by the basic region leucine zipper factor CCAAT/enhancer-binding protein A and the homeodomain factor Nkx2.1/thyroid transcription factor-1
复制标题
DOI：
10.1074/jbc.m201293200
复制
发表时间：
2002-10-04
影响因子：
4.8
通讯作者：
Nord, M
中科院分区：
文献类型：
--
作者：
Cassel, TN;Berg, T;Nord, M
碱性区域亮氨酸拉链转录因子 CCAAT/增强子结合蛋白 α (C/EBPα) 和同源域转录因子 Nkx2.1/甲状腺转录因子-1 对于正常的肺形态发生至关重要。 Nkx2.1 从肺发育开始就表达，而 C/EBPα 表达在后期才开启。 C/EBPα 的表达与具有分化依赖性表达模式的肺特异性蛋白的出现相关，例如 Clara 细胞分泌蛋白（分泌珠蛋白 1a1 (Scgb1a1)，CCSP）。在这项研究中，我们证明了 C/EBPalpha 和 Nkx2.1 在 CCSP 基因调控中的协同反式激活。我们表明，C/EBPα 和 Nkx2.1 的协同活性源自 CCSP 近端启动子中的顺式作用元件，并且协同作用依赖于 C/EBPα 和 Nkx2.1 的 NH2 末端反式激活结构域。我们的结果表明，C/EBPα 和 N-kx2.1 的合作是肺发育后期和成人肺中 CCSP 高水平肺上皮特异性表达的主要决定因素。
The basic region-leucine zipper transcription factor CCAAT/enhancer-binding protein alpha (C/EBPalpha) and the homeodomain transcription factor Nkx2.1/thyroid transcription factor-1 are essential for normal lung morphogenesis. Nkx2.1 is expressed from the onset of lung development, whereas C/EBPalpha expression is turned on at later stages. The expression of C/EBPalpha correlates to the appearance of lung-specific proteins with differentiation-dependent expression patterns, such as the Clara cell secretory protein (secretoglobin 1a1 (Scgb1a1), CCSP). In this study, we demonstrate synergistic transactivation by C/EBPalpha and Nkx2.1 in the regulation of the CCSP gene. We show that the synergistic activity of C/EBPalpha and Nkx2.1 originates from cis-acting elements in the proximal promoter of CCSP and that the synergism is dependent on NH2-terminal transactivation domains of C/EBPalpha and Nkx2.1. Our results suggest that the cooperation of C/EBPalpha and N-kx2.1 is a major determinant for the high level, lung epithelial-specific expression of CCSP during the later stages of lung development and in the adult lung.