YY1 positively regulates human UBIAD1 expression

Nobuaki Funahashi, Yoshihisa Hirota, Kimie Nakagawa, Natumi Sawada, Masato Watanabe, Yoshitomo Suhara, Toshio Okano

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K<inf>1</inf>) and a series of bacterial menaquionones (MK-n; vitamin K<inf>2</inf>). Menadione (vitamin K<inf>3</inf>) 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.

Original languageEnglish
Pages (from-to)238-244
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume460
Issue number2
DOIs
Publication statusPublished - 2015 May 1

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Keywords

  • Gene regulation
  • UBIAD1
  • Vitamin K
  • YY1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

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