Loop extrusion promotes an alternate pathway for isotype switching.
Loop extrusion promotes an alternate pathway for isotype switching.
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环路挤压促进了同型转换的替代途径。
DOI：
10.1016/j.celrep.2021.110059
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发表时间：
2021-11-23
期刊：
影响因子：
8.8
通讯作者：
Kenter AL
中科院分区：
文献类型：
--
作者：
Shen HM;Wuerffel R;Cantillo JF;Priyadarshi S;Lei X;Liang J;Wu YL;Kenter AL
类开关重组包括将Cμ恒定区替换为另一个下游的CH区。CSR是由激活诱导的胞苷脱氨酶(AID)介导的针对转录活性开关(S)区域的DNA断裂启动的。S区域启动子(PR)通过与共同锚定染色质环的Eμ和3‘Eα增强子结合来指导突触。我们报道了不对称环挤出允许3‘Eα沿着该位点跟踪并形成Pr-Pr-E相互作用，介导S下游区域之间的CSR，然后切换到供体Sμ。这一替代途径绕过了顺序转换，在没有IgG1表达的情况下产生了免疫球蛋白(Ig)E+B细胞。基于对B细胞亚群中诊断CSR产物的分析，我们确定了一种BCR阴性细胞中间体，它对有效的CSR至关重要。沈等人。据报道，3‘Eα通过单向环挤出沿着IgH基因座追踪，形成生殖系转录启动子(Pr)-Pr-E相互作用，介导了另一条CSR途径。确定了CSR的B细胞中间体，它们依赖于AID，表面bcr阴性，处于细胞周期的G1期。
Class-switch recombination (CSR) involves replacement of the Cμ constant region with another downstream CH region. CSR is initiated by activation-induced cytidine deaminase (AID)-mediated DNA breaks that are targeted to transcriptionally active switch (S) regions. S region promoters (Prs) direct synapsis by associating with the Eμ and 3′Eα enhancers that jointly anchor a chromatin loop. We report that asymmetric loop extrusion allows 3′Eα to track along the locus and form Pr-Pr-E interactions that mediate CSR between downstream S regions, followed by switching to donor Sμ. This alternative pathway bypasses sequential switching and creates immunoglobulin (Ig)E+ B cells in the absence of IgG1 expression. Based on the analysis of diagnostic CSR products in B cell subsets, we identify a BCR-negative cell intermediate that is pivotal to efficient CSR. Shen et al. report that 3′Eα tracks along the Igh locus via unidirectional loop extrusion to form germline transcript promoter (Pr)-Pr-E interactions that mediate an alternative CSR pathway. B cell intermediates of CSR are identified, which are AID-dependent, surface BCR-negative, and in the G1 phase of the cell cycle.
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影响因子：
64.5
作者：
Dekker J;Mirny L
通讯作者：
Mirny L
影响因子：
30.5
作者：
Manis, JP;Morales, JC;Carpenter, PB
通讯作者：
Carpenter, PB
影响因子：
15.3
作者：
Jung, S;Siebenkotten, G;Radbruch, A
通讯作者：
Radbruch, A
影响因子：
5.3
作者：
Garrett, FE;Emelyanov, AV;Birshtein, BK
通讯作者：
Birshtein, BK
DOI：
10.1073/pnas.95.20.11840
发表时间：
1998-09-29
影响因子：
11.1
作者：
Kingzette, M;Spieker-Polet, H;Knight, KL
通讯作者：
Knight, KL