Immunoglobulin kappa enhancers are differentially regulated at the level of chromatin structure.
Immunoglobulin kappa enhancers are differentially regulated at the level of chromatin structure.
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免疫球蛋白 kappa 增强剂在染色质结构水平上受到差异性调节。
DOI：
10.1016/j.molimm.2007.02.010
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发表时间：
2007
影响因子：
3.6
通讯作者：
Ganley-Leal,LisaM
中科院分区：
文献类型：
--
作者：
Nikolajczyk,BarbaraS;Sardi,SylviaH;Tumang,JosephR;Ganley-Leal,LisaM
κ 内含子和 κ3' 增强子协同调节 Igκ 位点的重组和转录。尽管这些增强子具有重叠的功能，但 κi 增强子似乎在受体编辑过程中占主导地位，而 κ3' 增强子可能对于启动 Igκ 种系转录以实现目标位点重组以及后期发育中的体细胞超突变更为重要。染色质结构的变化似乎可以调节这两种增强子，之前的报告表明，两种增强子仅在 B 谱系细胞中被包装成可接近的染色质结构。为什么这些增强子不能激活 pro-B 细胞中去甲基化的、可接近的、蛋白质相关的 Igκ 等位基因尚不清楚。此外，增强子如何重新激活受体编辑位点或定量促进 B 细胞超突变的功能尚不清楚。对小鼠原 B 细胞、前 B 细胞和脾 B 细胞中 Ig 增强子染色质结构的定量分析表明，κi 增强子在各种条件下都保持高度可接近的染色质结构。这种稳定的染色质结构反映了 Igμ 内含子增强子的高度易接近的结构特征，尽管事实上在 B 细胞发育过程中 Igμ 先于 Igκ 被激活。令人惊讶的是，对 κ3' 增强子的平行分析表明，其可接近的染色质结构明显不稳定，其特点是对环境条件变化敏感。这些数据出人意料地表明，κ 位点调节沿着 B 谱系细胞中的基因进行划分。此外，这些发现提出了以下可能性：κ3'增强子结构的环境依赖性调节是 B 细胞发育过程中 κ 激活变化的基础。
The κ intronic and the κ3′ enhancers synergize to regulate recombination and transcription of the Igκ locus. Although these enhancers have overlapping functions, the κi enhancer appears to predominate during receptor editing, while the κ3′ enhancer may be more important for initiating Igκ germline transcription to target locus recombination and, later in development, somatic hypermutation. Changes in chromatin structure appear to regulate both enhancers, and previous reports suggest that both enhancers are packaged into an accessible chromatin structure only in B lineage cells. Why these enhancers cannot activate the demethylated, accessible, protein-associated Igκ allele in pro-B cells is not known. Furthermore, how the enhancers function to reactivate the locus for receptor editing or to quantitatively promote hypermutation in B cells is vague. Quantitative analysis of Ig enhancer chromatin structure in murine pro-, pre-and splenic B cells demonstrated that the κi enhancer maintains a highly accessible chromatin structure under a variety of conditions. This stable chromatin structure mirrored the highly accessible structure characterizing the Igμ intronic enhancer, despite the fact that Igμ is activated prior to Igκ during B cell development. Surprisingly, parallel analysis of the κ3′ enhancer demonstrated its accessible chromatin structure is markedly unstable, as characterized by sensitivity to changes in environmental conditions. These data unexpectedly suggest that κ locus regulation is compartmentalized along the gene in B lineage cells. Furthermore, these findings raise the possibility that environmentally dependent regulation of κ3′ enhancer structure underlies changes in κ activation during B cell development.