title: YY1 positively regulates human UBIAD1 expression.
abstract: Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K1) and a series of bacterial menaquionones (MK-n; vitamin K2). Menadione (vitamin K3) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5' rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter.
authors.affiliation: Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan; Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. Electronic address: nfunahashi@ri.ncgm.go.jp.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Funahashi
authors.affiliation: Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan; Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Kimie
authors.initials: K
authors.lastname: Nakagawa
authors.affiliation: Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Natumi
authors.initials: N
authors.lastname: Sawada
authors.affiliation: Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Suhara
authors.affiliation: Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Okano
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D018076:DNA, Complementary; D004122:Dimethylallyltranstransferase / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic; D050986:YY1 Transcription Factor / Q000502:physiology*
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D004122:Dimethylallyltranstransferase; C425464:UBIAD1 protein, human
keywords: Gene regulation; UBIAD1; Vitamin K; YY1