Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development
Progressive activation of DNA replication initiation in large domains of the immunoglobulin heavy chain locus during B cell development
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DOI：
10.1016/j.molcel.2005.10.029
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发表时间：
2005-11-23
期刊：
影响因子：
16
通讯作者：
Schildkraut, CL
中科院分区：
文献类型：
--
作者：
Norio, P;Kosiyatrakul, S;Schildkraut, CL
在哺乳动物细胞中，组织特异性基因位点的复制被认为是在发育控制下。在这里，我们提供了直接的证据，存在发育调节的复制起点在细胞系和原代细胞。通过使用复制DNA的单分子分析（SMARD），我们确定了在Igh基因座内激活的各种共调节起源。这些起源簇可以跨越数百个酶，并且在B细胞发育期间被顺序激活，伴随着染色质结构和转录活性的发育调节变化。最后，我们表明，在B细胞发育过程中发生的DNA复制起始的变化，在D-J-C-3 'RR区域，发生在两个等位基因（表达和非表达）。
In mammalian cells, the replication of tissue-specific gene loci is believed to be under developmental control. Here, we provide direct evidence of the existence of developmentally regulated origins of replication in both cell lines and primary cells. By using single-molecule analysis of replicated DNA (SMARD), we identified various groups of coregulated origins that are activated within the Igh locus. These origin clusters can span hundreds of kilobases and are activated sequentially during B cell development, concomitantly with developmentally regulated changes in chromatin structure and transcriptional activity. Finally, we show that the changes in DNA replication initiation that take place during B cell development, within the D-J-C-3'RR region, occur on both alleles (expressed and nonexpressed).