title: MicroRNA-196b is transcribed from an autonomous promoter and is directly regulated by Cdx2 and by posterior Hox proteins during embryogenesis.
abstract: The miR-196 miRNA gene family located within the Hox gene clusters has been shown to function during embryogenesis and to be aberrantly expressed in various malignancies, including leukaemia, melanoma, and colorectal cancer. Despite its involvement in numerous biological processes, the control of miR-196 expression is still poorly defined. We identified the miR-196b promoter and found that the mature miR-196b originates from a large, non-coding primary transcript, which starts within an autonomous TATA box promoter and is not in physical continuity with either the Hoxa10 or Hoxa9 main primary transcripts. A ~680bp genomic fragment, spanning the pri-miR-196b transcription start site, is sufficient to recapitulate the neural tube expression pattern of miR-196 during embryogenesis. This region contains potential binding sites for Cdx and 5'Hox transcription factors. Two of these sites revealed to be necessary for neural tube expression and were bound in vivo by Cdx2 and Hoxd13. We show that Cdx2 is required for miR-196 expression and that both Cdx2 and 5'Hox, but not 3'Hox, are able to activate the miR-196b promoter. The possible role of Cdx2- and 5'Hox-mediated regulation of miR-196 expression in vertebrate anterior-posterior (AP) axis formation during embryogenesis is discussed.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 213/d, Modena 41125, Italy.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fantini
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 213/d, Modena 41125, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Salsi
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vitobello
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Rijli
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via G. Campi 213/d, Modena 41125, Italy. Electronic address: zappavigna.vincenzo@unimore.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Zappavigna
mesh_terms: D000818:Animals; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics; D000071616:CDX2 Transcription Factor; D002478:Cells, Cultured; D002642:Chick Embryo; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C487514:Cdx2 protein, mouse; C513184:HOXD13 protein, human; D018398:Homeodomain Proteins; C084118:Hoxd13 protein, mouse; C542543:MIRN196 microRNA, human; C000602251:MIRN196 microRNA, mouse; D035683:MicroRNAs; D014157:Transcription Factors
keywords: Cdx genes; Developmental biology; Hox genes; Post-transcriptional control mechanisms; Transcriptional regulation