Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through.
Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through.
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通过基因间DNA环和转录读取对miR-200c/141的调节。
DOI：
10.1038/ncomms9959
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发表时间：
2016-01-04
影响因子：
16.6
通讯作者：
Mechta-Grigoriou F
中科院分区：
文献类型：
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作者：
Batista L;Bourachot B;Mateescu B;Reyal F;Mechta-Grigoriou F
MiR-200家族成员参与了应激反应和卵巢肿瘤的发生。在这里，我们发现miR-200C/141的转录在所有被测试的生理条件下都与近端上游基因PTPN6(SHP1)的转录密切相关。PTPN6和miR-200C/141在转录水平上受两种互补机制的共同调控。首先，常规的PTPN6多聚腺苷信号的旁路允许下游miR-200C/141的转录。其次，PTPN6和miR-200C/141转录单位的启动子通过三维DNA环进行物理相互作用，并表现出类似的表观遗传调节。我们的发现强调了基因间miRNAs的转录是转录通读的新结果，并揭示了一种尚未探索的DNA环类型，将两个紧密定位的启动子联系在一起。这些机制与卵巢癌的应激反应以及miR-200C/141发挥关键作用的病理生理条件密切相关。MiR-141/200家族的microRNA控制氧化应激和对卵巢肿瘤发生的影响。在这里，作者证明miR-200C/141的转录是通过转录通读上游基因PTPN6，以及连接PTPN6和miR-200C/141启动子的DNA环来调节的。
The miR-200 family members have been implicated in stress responses and ovarian tumorigenesis. Here, we find that miR-200c/141 transcription is intimately linked to the transcription of the proximal upstream gene PTPN6 (SHP1) in all physiological conditions tested. PTPN6 and miR-200c/141 are transcriptionally co-regulated by two complementary mechanisms. First, a bypass of the regular PTPN6 polyadenylation signal allows the transcription of the downstream miR-200c/141. Second, the promoters of the PTPN6 and miR-200c/141 transcription units physically interact through a 3-dimensional DNA loop and exhibit similar epigenetic regulation. Our findings highlight that transcription of intergenic miRNAs is a novel outcome of transcriptional read-through and reveal a yet unexplored type of DNA loop associating two closely located promoters. These mechanisms have significant relevance in ovarian cancers and stress response, pathophysiological conditions in which miR-200c/141 exert key functions. The miR-141/200 familly of micro RNAs control oxidative stress and impact on ovarian tumorigenesis. Here the authors show that the transcription of miR-200c/141 is regulated through transcriptional read-through of the upstream gene PTPN6, and DNA looping linking the PTPN6 and miR-200c/141 promoters.