53BP1 Contributes to Igh Locus Chromatin Topology during Class Switch Recombination.
53BP1 Contributes to Igh Locus Chromatin Topology during Class Switch Recombination.
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DOI：
10.4049/jimmunol.1601947
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发表时间：
2017-03-15
期刊：
影响因子：
--
通讯作者：
Kenter AL
中科院分区：
文献类型：
--
作者：
Feldman S;Wuerffel R;Achour I;Wang L;Carpenter PB;Kenter AL
在B淋巴细胞中，免疫球蛋白类别转换重组（CSR）由激活诱导的胞苷脱氨酶（AID）诱导，其启动导致转换（S）区域中DNA双链断裂（DSB）形成的级联事件。DSB的分解通过形成S-S突触复合物进行。S-S突触由跨越Igh基因座的恒定区结构域的染色质环介导。S-S连接通过非同源末端连接DNA修复过程连接。CSR通过依赖于53 BP 1的染色体内环出和缺失机制发生。然而，53 BP 1促进缺失CSR和抑制反转转换事件的机制仍然未知。我们报道了53 BP 1在小鼠B细胞Igh染色质环中的一种新的结构作用。在不存在53 BP 1的情况下，Eμ和3 'E α增强子之间的长程相互作用显著减弱。相比之下，种系转录启动子：3 'E α环相互作用相互作用不受53 BP 1缺陷的影响。此外，53 BP 1染色质在Igh基因座位点的占据是B细胞特异性的，与组蛋白H4赖氨酸20标记相关，其受到染色质扩散的影响。因此，53 BP 1是Igh基因座的三维组织所必需的，并为53 BP 1执行缺失CSR之间的联系提供了合理的解释。
In B lymphocytes, immunoglobulin class switch recombination (CSR) is induced by activation induced cytidine deaminase (AID) which initiates a cascade of events leading to DNA double stand break (DSB) formation in switch (S) regions. Resolution of DSBs proceeds through formation of S-S synaptic complexes. S-S synapsis is mediated by a chromatin loop that spans the constant region domain of the Igh locus. S-S junctions are joined via a nonhomologous end joining DNA repair process. CSR occurs via an intra-chromosomal looping out and deletion mechanism that is 53BP1 dependent. However, the mechanism by which 53BP1 facilitates deletional CSR and inhibits inversional switching events remains unknown. We report a novel architectural role for 53BP1 in Igh chromatin looping in mouse B cells. Long range interactions between the Eμ and 3’Eα enhancers are significantly diminished in the absence of 53BP1. In contrast, germline transcript promoter:3’Eα looping interactions interactions are unaffected by 53BP1 deficiency. Furthermore, 53BP1 chromatin occupancy at sites in the Igh locus is B cell specific, correlated with histone H4 lysine 20 marks is subject to chromatin spreading. Thus, 53BP1 is required for three dimensional organization of the Igh locus and provides a plausible explanation for the link between 53BP1 enforcement of deletional CSR.
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影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
DOI：
10.1073/pnas.0901368106
发表时间：
2009-03-31
影响因子：
11.1
作者：
Kuang, Fei Li;Luo, Zhonghui;Scharff, Matthew D.
通讯作者：
Scharff, Matthew D.
影响因子：
16
作者：
Lou, ZK;Minter-Dykhouse, K;Chen, JJ
通讯作者：
Chen, JJ
影响因子：
5.3
作者：
Garrett, FE;Emelyanov, AV;Birshtein, BK
通讯作者：
Birshtein, BK
影响因子：
16
作者：
Bothmer A;Robbiani DF;Di Virgilio M;Bunting SF;Klein IA;Feldhahn N;Barlow J;Chen HT;Bosque D;Callen E;Nussenzweig A;Nussenzweig MC
通讯作者：
Nussenzweig MC