Department of Cell Physiology and Metabolism, University of Geneva, CMU, 1 Rue Michel Servet CH- 1211, Geneva 4, Switzerland.
J Membr Biol. 2012 Jun;245(5-6):263-73. doi: 10.1007/s00232-012-9447-1. Epub 2012 Jun 23.
The insulin-producing β cells of pancreatic islets are coupled by connexin36 (Cx36) channels. To investigate what controls the expression of this connexin, we have investigated its pattern during mouse pancreas development, and the influence of three transcription factors that are critical for β-cell development and differentiation. We show that (1) the Cx36 gene (Gjd2) is activated early in pancreas development and is markedly induced at the time of the surge of the transcription factors that determine β-cell differentiation; (2) the cognate protein is detected about a week later and is selectively expressed by β cells throughout the prenatal development of mouse pancreas; (3) a 2-kbp fragment of the Gjd2 promoter, which contains three E boxes for the binding of the bHLH factor Beta2/NeuroD1, ensures the expression of Cx36 by β cells; and (4) Beta2/NeuroD1 binds to these E boxes and, in the presence of the E47 ubiquitous cofactor, transactivates the Gjd2 promoter. The data identify Cx36 as a novel early marker of β cells and as a target of Beta2/NeuroD1, which is essential for β-cell development and differentiation.
胰岛的胰岛素分泌β细胞通过连接蛋白 36（Cx36）通道偶联。为了研究是什么控制这种连接蛋白的表达，我们研究了它在小鼠胰腺发育过程中的表达模式，以及对三个对β细胞发育和分化至关重要的转录因子的影响。我们发现：(1) Cx36 基因（Gjd2）在胰腺发育早期被激活，并在决定β细胞分化的转录因子激增时显著诱导；(2) 大约一周后检测到相应的蛋白质，并在小鼠胰腺的整个产前发育过程中选择性地由β细胞表达；(3) Gjd2 启动子的 2-kbp 片段，包含三个结合 bHLH 因子 Beta2/NeuroD1 的 E 盒，确保了β细胞表达 Cx36；(4) Beta2/NeuroD1 结合这些 E 盒，并在通用的 E47 共因子存在下，反式激活 Gjd2 启动子。这些数据将 Cx36 鉴定为β细胞的一个新的早期标志物，也是 Beta2/NeuroD1 的靶标，后者对于β细胞的发育和分化是必不可少的。
