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

被引:200
作者
Lee, Youn-Bok [1 ]
Bantounas, Ioannis [1 ]
Lee, Do-Young [1 ]
Phylactou, Leonidas [2 ]
Caldwell, Maeve A. [1 ]
Uney, James B. [1 ]
机构
[1] Univ Bristol, Henry Wellcome Labs Integrated Neurosci & Endocri, Bristol BS1 3NY, Avon, England
[2] Cyprus Inst Neurol & Genet, CY-1683 Nicosia, Cyprus
基金
英国惠康基金;
关键词
HUMAN OVARIAN-CANCER; TRANSCRIPTION FACTORS; EXPRESSION; MOUSE; PROTEIN; CELLS; GENE; METASTASIS; DROSOPHILA; MICRORNAS;
D O I
10.1093/nar/gkn920
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:123 / 128
页数:6
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