Defining Transcriptional Regulatory Mechanisms for Primary let-7 miRNAs.
Defining Transcriptional Regulatory Mechanisms for Primary let-7 miRNAs.
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DOI：
10.1371/journal.pone.0169237
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Lowry WE
中科院分区：
文献类型：
--
作者：
Gaeta X;Le L;Lin Y;Xie Y;Lowry WE
Let-7家族的miRNAs已被证明控制着从线虫到人类的生物体的发育时间；它们在发育过程中的几个基本细胞过程中的功能也被很好地保守。许多研究已经确定了let-7产生的转录后调控的几个步骤：从pri-miRNA到前miRNA，再到针对内源mRNAs降解或翻译抑制的成熟miRNA。较不明确的是let-7的pri-miRNAs的转录调控模式。Let-7 pri-miRNAs以多顺反子的方式在长转录本中表达，新的转录本基于染色质相关的RNA测序。分化后，我们发现一些let-7 pri-miRNAs在转录水平上受到调控，而另一些似乎是结构性转录的。使用表观遗传路线图数据库，我们进一步注释了每个多顺反子的调控元件，确定了推定的启动子和增强子。探索这些转录因子结合位点的调控元件，发现了在启动子和增强子区域调控let-7转录的因子，并确定了这类重要miRNAs的新调控机制。
The let-7 family of miRNAs have been shown to control developmental timing in organisms from C. elegans to humans; their function in several essential cell processes throughout development is also well conserved. Numerous studies have defined several steps of post-transcriptional regulation of let-7 production; from pri-miRNA through pre-miRNA, to the mature miRNA that targets endogenous mRNAs for degradation or translational inhibition. Less-well defined are modes of transcriptional regulation of the pri-miRNAs for let-7. let-7 pri-miRNAs are expressed in polycistronic fashion, in long transcripts newly annotated based on chromatin-associated RNA-sequencing. Upon differentiation, we found that some let-7 pri-miRNAs are regulated at the transcriptional level, while others appear to be constitutively transcribed. Using the Epigenetic Roadmap database, we further annotated regulatory elements of each polycistron identified putative promoters and enhancers. Probing these regulatory elements for transcription factor binding sites identified factors that regulate transcription of let-7 in both promoter and enhancer regions, and identified novel regulatory mechanisms for this important class of miRNAs.
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影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
DOI：
10.1073/pnas.1220176110
发表时间：
2013-08-06
影响因子：
11.1
作者：
Cimadamore, Flavio;Amador-Arjona, Alejandro;Terskikh, Alexey V.
通讯作者：
Terskikh, Alexey V.
影响因子：
16.2
作者：
Li, SG;Mo, ZQ;Xiang, MQ
通讯作者：
Xiang, MQ
影响因子：
11.8
作者：
Grosshans, H;Johnson, T;Slack, FJ
通讯作者：
Slack, FJ
影响因子：
4.3
作者：
Kawahara H;Imai T;Okano H
通讯作者：
Okano H