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

Fingerprint

Vitamin K 3
Vitamin K
Vitamin K 1
Messenger RNA
Dimethylallyltranstransferase
Vitamin K 2
Cloning
Bioactivity
Coagulation
Small Interfering RNA
Chromatin
Amplification
Tumors
Assays
Brain
Bone
Blood
Nucleotides
Complementary DNA
Genes

Keywords

  • Gene regulation
  • UBIAD1
  • Vitamin K
  • YY1

ASJC Scopus subject areas

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

Cite this

YY1 positively regulates human UBIAD1 expression. / Funahashi, Nobuaki; Hirota, Yoshihisa; Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato; Suhara, Yoshitomo; Okano, Toshio.

In: Biochemical and Biophysical Research Communications, Vol. 460, No. 2, 01.05.2015, p. 238-244.

Research output: Contribution to journalArticle

Funahashi, Nobuaki ; Hirota, Yoshihisa ; Nakagawa, Kimie ; Sawada, Natumi ; Watanabe, Masato ; Suhara, Yoshitomo ; Okano, Toshio. / YY1 positively regulates human UBIAD1 expression. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 460, No. 2. pp. 238-244.
@article{1da7f8f4490c45e3a58fc95afb9b554a,
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.",
keywords = "Gene regulation, UBIAD1, Vitamin K, YY1",
author = "Nobuaki Funahashi and Yoshihisa Hirota and Kimie Nakagawa and Natumi Sawada and Masato Watanabe and Yoshitomo Suhara and Toshio Okano",
year = "2015",
month = "5",
day = "1",
doi = "10.1016/j.bbrc.2015.03.018",
language = "English",
volume = "460",
pages = "238--244",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - YY1 positively regulates human UBIAD1 expression

AU - Funahashi, Nobuaki

AU - Hirota, Yoshihisa

AU - Nakagawa, Kimie

AU - Sawada, Natumi

AU - Watanabe, Masato

AU - Suhara, Yoshitomo

AU - Okano, Toshio

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - Gene regulation

KW - UBIAD1

KW - Vitamin K

KW - YY1

UR - http://www.scopus.com/inward/record.url?scp=84937758063&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84937758063&partnerID=8YFLogxK

U2 - 10.1016/j.bbrc.2015.03.018

DO - 10.1016/j.bbrc.2015.03.018

M3 - Article

VL - 460

SP - 238

EP - 244

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 2

ER -