Department of Microbiology and Immunology, University of Illinois College of Medicine, 835 S. Wolcott, Chicago, IL 60612-7344, USA.
Semin Immunol. 2012 Aug;24(4):281-6. doi: 10.1016/j.smim.2012.06.001. Epub 2012 Jul 10.
Activation induced deaminase (AID) is globally targeted to immunoglobulin loci, preferentially focused to switch (S) regions and variable (V) regions, and prone to attack hotspot motifs. Nevertheless, AID deamination is not exclusive to Ig loci and the rules regulating AID targeting remain unclear. Transcription is critically required for class switch recombination and somatic hypermutation. Here, I consider the unique features associated with S region transcription leading to RNA polymerase II pausing, that in turn promote the introduction of activating chromatin remodeling, histone modifications and recruitment of AID to targeted S regions. These findings allow for a better understanding of the interplay between transcription, AID targeting and mistargeting to Ig and non-Ig loci.
激活诱导脱氨酶 (AID) 被全局靶向免疫球蛋白基因座,优先集中于开关 (S) 区和可变 (V) 区,并易于攻击热点基序。然而,AID 脱氨酶并非仅限于 Ig 基因座,调节 AID 靶向的规则仍不清楚。转录对于类别转换重组和体细胞超突变至关重要。在这里,我考虑了与 S 区转录相关的独特特征,导致 RNA 聚合酶 II 暂停,这反过来又促进了激活染色质重塑、组蛋白修饰以及 AID 向靶向 S 区的募集。这些发现有助于更好地理解转录、AID 靶向以及 Ig 和非 Ig 基因座的错误靶向之间的相互作用。