Twist-1 regulates the miR-199a/214 cluster during development.

Twist-1 regulates the miR-199a/214 cluster during development.
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Twist-1在开发过程中调节miR-199a/214群集。

DOI:
10.1093/nar/gkn920
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发表时间:
2009-01
影响因子:
14.9
通讯作者:
Uney JB
Uney JB
中科院分区:
生物学2区
文献类型:
--
作者:
Lee YB;Bantounas I;Lee DY;Phylactou L;Caldwell MA;Uney JB

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已知microRNA调节发育过程,但其调节机制在很大程度上仍不清楚。我们显示转录因子Twist-1驱动编码miR-199 a和miR-214簇的7.9 kb非编码RNA转录物(来自发动蛋白-3基因内含子)的表达。我们还发现,用shRNAs敲低Twist-1降低了miR-199 a/214水平,Twist-1结合了E-Box启动子基序,从而在发育过程中调节这些miRNAs的表达。HIF-1(已知介导Twist-1转录)、miR-199 a和miR-214的表达在E12.5达到最大,并且miRNAs特异性地表达于小鼠小脑、中脑、鼻突和前后肢芽。这项研究表明,miR 199 a/214簇的表达是由Twist-1通过E-Box启动子元件控制的,并支持这些miRNA作为控制特定神经细胞群发育的途径中的新型中间体的作用。
MicroRNAs are known to regulate developmental processes but their mechanism of regulation remains largely uncharacterized. We show the transcription factor Twist-1 drives the expression of a 7.9-kb noncoding RNA transcript (from the Dynamin-3 gene intron) that encodes a miR-199a and miR-214 cluster. We also show that knocking down Twist-1 with shRNAs decreased miR-199a/214 levels and that Twist-1 bound an E-Box promoter motif to developmentally regulate the expression of these miRNAs. The expression of HIF-1 (known to mediate Twist-1 transcription), miR-199a and miR-214 was maximal at E12.5 and the miRNAs were expressed specifically in mouse cerebellum, midbrain, nasal process and fore- and hindlimb buds. This study shows the expression of the miR199a/214 cluster is controlled by Twist-1 via an E-Box promoter element and supports a role for these miRNAs as novel intermediates in the pathways controlling the development of specific neural cell populations.
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