title: Twist-1 regulates the miR-199a/214 cluster during development.
abstract: 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.
authors.affiliation: The Henry-Wellcome Laboratories for Integrated Neuroscience and Endocrinology, University of Bristol, Bristol, UK.
authors.forename: Youn-Bok
authors.initials: YB
authors.lastname: Lee
authors.forename: Ioannis
authors.initials: I
authors.lastname: Bantounas
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Lee
authors.forename: Leonidas
authors.initials: L
authors.lastname: Phylactou
authors.forename: Maeve A
authors.initials: MA
authors.lastname: Caldwell
authors.forename: James B
authors.initials: JB
authors.lastname: Uney
mesh_terms: 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*
chemical_list: 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