Tanaka K, Barra Y, Isselbacher K J, Khoury G, Jay G
Proc Natl Acad Sci U S A. 1986 Oct;83(20):7598-602. doi: 10.1073/pnas.83.20.7598.
The H-2 class I genes encode cell-surface glycoproteins that play a critical role in the immune presentation of aberrant cells. The Q10 class I gene, however, encodes a secreted glycoprotein that is highly homologous to the membrane-bound molecules. While the H-2 genes are activated in all tissue types, the expression of the Q10 gene is restricted to only the liver. Analysis of DNA from different tissues revealed a unique methylation profile for the Q10 gene in liver. Developmental activation of this gene in newborn mice is also reflected by a coordinated temporal change in DNA methylation. By comparing the methylation profiles between congenic mice, which differed in their levels of expression of the Q10 gene, it is observed that methylation at the 3'-flanking region correlates with expression. Methylations were at both CG and CC sequences. Since treatment of newborns with 5-azacytidine, which led to inhibition of methylation, resulted in the suppression of Q10, we conclude that hypermethylation in the 3'-flanking region is responsible, at least in part if not in full, for the activation of the Q10 gene in the liver.
H-2 I类基因编码细胞表面糖蛋白，这些糖蛋白在异常细胞的免疫呈递中起关键作用。然而，Q10 I类基因编码一种分泌型糖蛋白，它与膜结合分子高度同源。虽然H-2基因在所有组织类型中都被激活，但Q10基因的表达仅限于肝脏。对不同组织的DNA分析揭示了肝脏中Q10基因独特的甲基化模式。新生小鼠中该基因的发育激活也反映在DNA甲基化的协同时间变化上。通过比较Q10基因表达水平不同的同源基因小鼠之间的甲基化模式，观察到3'侧翼区域的甲基化与表达相关。甲基化发生在CG和CC序列上。由于用5-氮杂胞苷处理新生小鼠会导致甲基化抑制，进而导致Q10表达受抑制，我们得出结论，3'侧翼区域的高甲基化至少部分（如果不是全部）负责肝脏中Q10基因的激活。
