淋巴细胞是哺乳动物唯一能发生体细胞基因组变化的一类细胞,淋巴细胞在发育过程中通过V(D) J重组获得成熟的特异的抗原受体基因,实现了免疫细胞抗原识别惊人的多样性.关于V(D) J重组的调控机制一直是免疫学研究的重要问题,然而直到将表观遗传学研究引入这一领域,综合遗传学和表观遗传学的研究才真正揭示V(D) J重组精细的调控机制.综述了新近发现的V(D) J重组过程中重要的表观遗传学调控机制,如CpG甲基化,组蛋白修饰,核小体重塑及核拓扑学变化.
During lymphocyte development antigen receptor genes undergo V(D)J recombination to obtain antigen binding specificity and diversity. This process is not only controlled by genetic factors, such as tissue- and stage- specificity of RAG-1/2 protein, germline transcriptional activity and ACEs, but also regulated at epigenetic level. The chromatin accessibility of recombinase is associated with the chromatin configuration around the targeted gene segments. Thus, activation of V(D)J recombination requires the recruitment of remodeling complexes for changing the accessibility in the localized chromatin. Moreover, docking of remodeling complexes, which serve for creating active chromatin environment, relies on certain patterns of chromatin modification. Some recent findings regarding epigenetic regulation mechanisms in V(D)J recombination, such as CpG methylation, histone modification, nucleosome remodeling and nuclear topology were reviewed.
郑超固,阎锡蕴.抗原受体基因重组的表观遗传学调控研究新进展[J].生物化学与生物物理进展,2008,35(2):133-142
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