Molecular mechanisms for class switch recombination and somatic hypermutation of immunoglobulin genes

AID是免疫球蛋白基因改变的核心分子；它的活性被认为与各种类型细胞的肿瘤发生有关。我们已经分析了Aicda基因及其周围的调控元件，并确定了增强子和沉默因子的必要DNA区域。染色质免疫沉淀法证实了与这些元件结合的某些因子。我们还发现组蛋白伴侣Spt6与AID相关，并参与免疫球蛋白基因的类切换重组。重组修复步骤所需的AID的C-末端。这些发现为理解AID在正常和异常情况下的分子机制提供了重要的见解，这两种机制分别对抗体多样性和肿瘤发生至关重要。

AID is the molecule central for Immunoglobulin gene alteration ; its activity is believed to be involved in tumorigenesis in various types of cells. We have analyzed the regulatory elements in/around Aicda, the gene for AID and have determined essential DNA regions for enhancer and silencer. Some factors that bind to these elements were confirmed by chromatin immunoprecipitation. We also found that Spt6, a histone chaperon, associates with AID and it is involved in class switch recombination of immunoglobulin gene. A C-terminus of AID required for the repairing step of the recombination. These findings provide an important insight for understanding the molecular mechanisms of AID in normal and abnormal situation that are essential for antibody diversity and tumorigenesis, respectively.