Twist-1 regulates the miR-199a/214 cluster during development.
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.
Lee
Youn-Bok
YB
The Henry-Wellcome Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, Bristol, UK.
Bantounas
Ioannis
I
Lee
Do-Young
DY
Phylactou
Leonidas
L
Caldwell
Maeve A
MA
Uney
James B
JB
D000818:Animals; D034286:Dynamin III / Q000235:genetics; D024721:E-Box Elements; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051879:Twist-Related Protein 1 / Q000378:metabolism*
D035683:MicroRNAs; C534780:Mirn199 microRNA, mouse; C534781:Mirn214 microRNA, mouse; D009687:Nuclear Proteins; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse; D034286:Dynamin III