1] Université de Limoges, CRIBL, UMR 7276, Limoges 87000, France [2] CNRS UMR 7276, Limoges 87000, France.
CNRS et Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097, Sophia Antipolis 06560, France.
Nat Commun. 2015 May 11;6:7084. doi: 10.1038/ncomms8084.
In mature B cells, class switch recombination (CSR) replaces the expressed constant Cμ gene with a downstream C(H) gene. How the four transcriptional enhancers of the IgH 3' regulatory region (3'RR) control CSR remains an open question. We have investigated IgG1 CSR in 3'RR-deficient mice. Here we show that the 3'RR enhancers target the S(γ1) acceptor region (and poorly the S(μ) donor region) by acting on epigenetic marks, germline transcription, paused RNA Pol II recruitment, R loop formation, AID targeting and double-strand break generation. In contrast, location and diversity of S(μ)-S(γ1) junctions are not affected by deletion of the 3'RR enhancers. Thus, the 3'RR controls the first steps of CSR by priming the S acceptor region but is not implicated in the choice of the end-joining pathway.
在成熟 B 细胞中，类别转换重组（CSR）用下游的 C(H) 基因替换表达的恒定 Cμ 基因。IgH 3'调控区（3'RR）的四个转录增强子如何控制 CSR 仍然是一个悬而未决的问题。我们已经研究了 3'RR 缺陷型小鼠中的 IgG1 CSR。在这里，我们通过作用于表观遗传标记、种系转录、暂停的 RNA Pol II 募集、R 环形成、AID 靶向和双链断裂产生，表明 3'RR 增强子将 S(γ1)接受体区域作为靶点（而对 S(μ)供体区域的靶向作用较差）。相比之下，3'RR 增强子缺失并不影响 S(μ)-S(γ1) 接头的位置和多样性。因此，3'RR 通过启动 S 接受体区域来控制 CSR 的第一步，但不参与末端连接途径的选择。
