Liao L, Trouba K J, Vorce R L
Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Placenta. 1998 Mar-Apr;19(2-3):225-30. doi: 10.1016/s0143-4004(98)90012-1.
This study was based on the hypothesis that both primary sequence and methylation status of the GTPase activating protein (GAP) gene limits expression of p100 GAP to primate placenta. Due to alternate splicing, a 65-bp insert appears between the first and second coding exons of p100 GAP mRNA, and translation of p100 GAP initiates within this insert. Examination of the sequence surrounding the 65-bp insert revealed that the monkey GAP gene contained both the 3' splice donor site and the internal start codon, whereas the mouse GAP gene contained neither. To address p100 GAP tissue specificity, the methylation status of the GAP gene was examined. Site-specific demethylation was found to correlate with synthesis of p100 GAP, suggesting that methylation regulates the expression of different GAP isoforms. The results of this study provide a mechanistic basis for the observation that p100 GAP is synthesized only in primate placenta and suggest that its expression is regulated, in part, by gene methylation.
GTP酶激活蛋白（GAP）基因的一级序列和甲基化状态限制了p100 GAP在灵长类胎盘组织中的表达。由于可变剪接，在p100 GAP mRNA的第一个和第二个编码外显子之间出现了一个65bp的插入片段，并且p100 GAP的翻译在此插入片段内起始。对围绕65bp插入片段的序列进行检查发现，猴GAP基因同时包含3'剪接供体位点和内部起始密码子，而小鼠GAP基因两者均无。为了研究p100 GAP的组织特异性，对GAP基因的甲基化状态进行了检查。发现位点特异性去甲基化与p100 GAP的合成相关，这表明甲基化调节不同GAP亚型的表达。本研究结果为p100 GAP仅在灵长类胎盘中合成这一现象提供了机制基础，并表明其表达部分受基因甲基化调控。
