Mechanisms of MLL gene rearrangement:: site-specific DNA cleavage within the breakpoint cluster region is independent of chromosomal context
Mechanisms of MLL gene rearrangement:: site-specific DNA cleavage within the breakpoint cluster region is independent of chromosomal context
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DOI：
10.1093/hmg/10.22.2481
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发表时间：
2001-10-15
影响因子：
3.5
通讯作者：
Aplan, PD
中科院分区：
文献类型：
--
作者：
Stanulla, M;Chhalliyil, P;Aplan, PD
在与细胞凋亡相关的高阶染色质断裂过程中，染色体带 11q23 处的 MLL 基因在其断点簇区域 (bcr) 内的独特位点被特异性切割。我们现在表明，可以在整合到正常染色体背景之外的基因组中的外源 MLL bcr 片段中以及在包含 MLL bcr 片段的染色体外附加体中检测到相同的特定 DNA 切割事件。我们还表明，在支架相关区域 (SAR) 测定中进行测试时，MLL bcr 的附加型或随机整合副本的行为与内源性 MLL bcr 相似。此外，引入人类细胞的附加型鼠MLL bcr在与内源性鼠MLL bcr相同的位点被切割；这种游离型小鼠 MLL bcr 在人类细胞中也起到 SAR 的作用。我们的结论是，核 DNA 支架附着以及位点特异性 DNA 切割都可以通过 MLL bcr 中包含的序列进行指导，并且使用附加型穿梭载体研究这些事件是可行的。
The MLL gene at chromosome band 11q23 is specifically cleaved at a unique site within its breakpoint cluster region (bcr) during the higher order chromatin fragmentation associated with apoptosis. We now show that the same specific DNA cleavage event can be detected in an exogenous MLL bcr fragment that is integrated into the genome outside of its normal chromosomal context, as well as in an extrachromosomal episome containing an MLL bcr fragment. We also show that episomal or randomly integrated copies of the MLL bcr behave similar to the endogenous MLL bcr when tested in a scaffold-associated region (SAR) assay. Furthermore, an episomal murine MLL bcr introduced into human cells is cleaved at the same site as the endogenous murine MLL bcr; this episomal murine MLL bcr also functions as a SAR in human cells. We conclude that both nuclear DNA scaffold attachment as well as site-specific DNA cleavage can be directed by sequences contained within the MLL bcr, and that it is feasible to study these events using episomal shuttle vectors.