Martin Karen M, Ellis Peter D, Metcalfe James C, Kemp Paul R
Section of Cardiovascular Biology, Department of Biochemistry, University of Cambridge, Building O, Downing Site, Cambridge CB2 1QW, U.K.
Biochem J. 2003 Oct 15;375(Pt 2):457-63. doi: 10.1042/BJ20030870.
We have previously identified a C2H2 zinc-finger transcription factor [BTEB3 (basal transcription element-binding protein 3)/KLF13 (Krüppel-like factor 13)] that activates the minimal promoter for the smooth muscle-specific SM22alpha gene in other types of cell. We show that recombinant BTEB3 binds to three TGGG motifs in the minimal SM22alpha promoter. By mutation analysis, only one of these boxes is required for BTEB3-dependent promoter activation in P19 cells and BTEB3 activates or inhibits reporter gene expression depending on the TGGG box to which it binds. Transient transfection experiments show that BTEB3 also activates reporter gene expression from the SM22alpha promoter in VSMCs (vascular smooth muscle cells). Similar studies showed that BTEB3 did not activate expression from the promoter regions of the smooth muscle myosin heavy chain or smooth muscle alpha-actin promoters, which contain similar sequences, implying that promoter activation by BTEB3 is selective. The expression of BTEB3 is readily detectable in VSMCs in vitro and is modulated in response to injury in vivo.
我们之前鉴定出一种C2H2锌指转录因子[BTEB3（基础转录元件结合蛋白3）/KLF13（类Krüppel因子13）]，它可在其他类型细胞中激活平滑肌特异性SM22α基因的最小启动子。我们发现重组BTEB3可与最小SM22α启动子中的三个TGGG基序结合。通过突变分析，在P19细胞中，这些框中只有一个是BTEB3依赖性启动子激活所必需的，并且BTEB3根据其结合的TGGG框激活或抑制报告基因表达。瞬时转染实验表明，BTEB3还可激活血管平滑肌细胞（VSMC）中SM22α启动子的报告基因表达。类似研究表明，BTEB3不会激活平滑肌肌球蛋白重链或平滑肌α-肌动蛋白启动子区域的表达，这些启动子区域含有相似序列，这意味着BTEB3对启动子的激活具有选择性。BTEB3的表达在体外培养的VSMC中易于检测到，并且在体内对损伤有反应性调节。
