V(D)J复合
染色质
生物
重组
重组酶
遗传学
CTCF公司
重组信号序列
分子生物学
基因座(遗传学)
基因
染色体构象捕获
发起人
重组激活基因
增强子
转录因子
基因表达
作者
Brittney M. Allyn,Katharina E. Hayer,Clement Oyeniran,Vincent Nganga,Kyutae D. Lee,Bikash Mishra,Ahmet Saçan,Eugene M. Oltz,Craig H. Bassing
摘要
The dynamic folding of genomes regulates numerous biological processes, including antigen receptor (AgR) gene assembly. We show that, unlike other AgR loci, homotypic chromatin interactions and bidirectional chromosome looping both contribute to structuring Tcrb for efficient long-range V(D)J recombination. Inactivation of the CTCF binding element (CBE) or promoter at the most 5'Vβ segment (Trbv1) impaired loop extrusion originating locally and extending to DβJβ CBEs at the opposite end of Tcrb. Promoter or CBE mutation nearly eliminated Trbv1 contacts and decreased RAG endonuclease-mediated Trbv1 recombination. Importantly, Trbv1 rearrangement can proceed independent of substrate orientation, ruling out scanning by DβJβ-bound RAG as the sole mechanism of Vβ recombination, distinguishing it from Igh. Our data indicate that CBE-dependent generation of loops cooperates with promoter-mediated activation of chromatin to juxtapose Vβ and DβJβ segments for recombination through diffusion-based synapsis. Thus, the mechanisms that fold a genomic region can influence molecular processes occurring in that space, which may include recombination, repair, and transcriptional programming.
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