A p53 enhancer region regulates target genes through chromatin conformations in cis and in trans

A p53 enhancer region regulates target genes through chromatin conformations in cis and in trans
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DOI:
10.1101/gad.225565.113
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发表时间:
2013-11-15
影响因子:
10.5
通讯作者:
Abrams, John M.
Abrams, John M.
中科院分区:
生物学1区
文献类型:
--
作者:
Link, Nichole;Kurtz, Paula;Abrams, John M.

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我们研究了p53增强子如何在体内传递调控信息。使用基因消融与数字染色体构象捕获和荧光原位杂交,我们发现,果蝇p53增强子区域(称为p53响应元件[p53RE])物理接触顺式和跨着丝粒的目标,以控制在这些网站的应激反应转录。此外,当放置在异位基因组位置时,跨越该元件的片段重新建立染色质接触并部分恢复对缺乏天然p53 RE的突变体的靶基因调控。因此,一个确定的p53增强子区域足以进行长距离的染色质相互作用,使多基因调控。
We examined how a p53 enhancer transmits regulatory information in vivo. Using genetic ablation together with digital chromosome conformation capture and fluorescent in situ hybridization, we found that a Drosophila p53 enhancer region (referred to as the p53 response element [p53RE]) physically contacts targets in cis and across the centromere to control stress-responsive transcription at these sites. Furthermore, when placed at ectopic genomic positions, fragments spanning this element re-established chromatin contacts and partially restored target gene regulation to mutants lacking the native p53RE. Therefore, a defined p53 enhancer region is sufficient for long-range chromatin interactions that enable multigenic regulation.