Gene Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224, USA.
Cell. 2011 Oct 14;147(2):332-43. doi: 10.1016/j.cell.2011.08.049. Epub 2011 Oct 6.
The immunoglobulin heavy-chain (IgH) gene locus undergoes radial repositioning within the nucleus and locus contraction in preparation for gene recombination. We demonstrate that IgH locus conformation involves two levels of chromosomal compaction. At the first level, the locus folds into several multilooped domains. One such domain at the 3' end of the locus requires an enhancer, Eμ; two other domains at the 5' end are Eμ independent. At the second level, these domains are brought into spatial proximity by Eμ-dependent interactions with specific sites within the V(H) region. Eμ is also required for radial repositioning of IgH alleles, indicating its essential role in large-scale chromosomal movements in developing lymphocytes. Our observations provide a comprehensive view of the conformation of IgH alleles in pro-B cells and the mechanisms by which it is established.
免疫球蛋白重链（IgH）基因座在核内经历放射状重定位和基因座收缩，为基因重组做准备。我们证明了 IgH 基因座构象涉及两个层次的染色体紧缩。在第一个层次上，基因座折叠成几个多环结构域。位于基因座 3' 端的一个这样的结构域需要一个增强子 Eμ；另外两个位于 5' 端的结构域与 Eμ 无关。在第二个层次上，这些结构域通过与 V（H）区域内特定位点的 Eμ 依赖性相互作用而接近空间。Eμ 也需要 IgH 等位基因的放射状重定位，这表明它在发育淋巴细胞中的大规模染色体运动中起着至关重要的作用。我们的观察提供了一个全面的视角，了解了前 B 细胞中 IgH 等位基因的构象及其建立的机制。
