Peters Jan-Michael
Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, 1030 Vienna, Austria.
Curr Opin Cell Biol. 2021 Jun;70:75-83. doi: 10.1016/j.ceb.2020.11.007. Epub 2021 Jan 7.
'Structural maintenance of chromosomes' (SMC) complexes are required for the folding of genomic DNA into loops. Theoretical considerations and single-molecule experiments performed with the SMC complexes cohesin and condensin indicate that DNA folding occurs via loop extrusion. Recent work indicates that this process is essential for the assembly of antigen receptor genes by V(D)J recombination in developing B and T cells of the vertebrate immune system. Here, I review how recent studies of the mouse immunoglobulin heavy chain locus Igh have provided evidence for this hypothesis and how the formation of chromatin loops by cohesin and regulation of this process by CTCF and Wapl might ensure that all variable gene segments in this locus (V segments) participate in recombination with a re-arranged DJ segment, to ensure generation of a maximally diverse repertoire of B-cell receptors and antibodies.
“染色体结构维持”（SMC）复合物是基因组DNA折叠成环所必需的。对SMC复合物黏连蛋白和凝聚素进行的理论思考和单分子实验表明，DNA折叠通过环挤压发生。最近的研究表明，这一过程对于脊椎动物免疫系统发育中的B细胞和T细胞通过V（D）J重组组装抗原受体基因至关重要。在此，我将回顾近期对小鼠免疫球蛋白重链基因座Igh的研究如何为这一假说提供证据，以及黏连蛋白形成染色质环的过程以及CTCF和Wapl对该过程的调控如何确保该基因座中的所有可变基因片段（V片段）与重排的DJ片段参与重组，以确保产生最大限度多样化的B细胞受体和抗体库。
