PMID- 20945371
OWN - NLM
STAT- MEDLINE
DCOM- 20110516
LR  - 20131121
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 226
IP  - 6
DP  - 2011 Jun
TI  - Divalent metal transporter 1 is a hypoxia-inducible gene.
PG  - 1596-603
LID - 10.1002/jcp.22485 [doi]
AB  - Our recent study revealed a high correlation between the expression of 
      hypoxia-inducible factor-1 (HIF-1) alpha and divalent metal transporter 1 (DMT1) 
      in HepG2 cells treated with chemical or physical hypoxia. We therefore speculated 
      that DMT1 might be one of the target genes of HIF-1. Here, we characterized the 
      DMT1 exon1B promoter region and identified a functional hypoxia response element 
      (HRE, 5'-TCAGTACCTAACGTGGCGCCACGGC-3') harboring a binding site for HIF-1. We 
      demonstrated that hypoxia-dependent activation of a luciferase reporter gene in 
      transfected HepG2 cells is mediated by a fragment of human DMT1 exon1B promoter 
      containing the putative HRE sequence. We also showed that the HIF-1 binding site 
      (HBS) is in DMT1 exon1B promoter with the core sequence of HRE (5'-ACGTG-3') at 
      -327 to -323 relative to the transcription start site of the human DMT1 exon1B 
      gene. The mutation of this sequence prevented stimulation of luciferase activity. 
      Electrophoretic mobility shift assays revealed that the HRE sequence found in the 
      DMT1 gene promoter was bound by HIF-1. In addition, we provide evidence that 
      hypoxia could significantly increase ferrous uptake, while the silencing of total 
      DMT1 by RNA interference down-regulates DMT1 expression and ferrous uptake in 
      HepG2 cells. We conclude that DMT1 is a hypoxia-inducible gene.
CI  - Copyright (c) 2010 Wiley-Liss, Inc.
FAU - Qian, Zhong-Ming
AU  - Qian ZM
AD  - Laboratory of Iron Metabolism, Department of Applied Biology and Chemical 
      Technology, Hong Kong Polytechnic University, Kowloon, Hong Kong. 
      bczmqian@polyu.edu.hk
FAU - Wu, Xiao Mei
AU  - Wu XM
FAU - Fan, Ming
AU  - Fan M
FAU - Yang, Lin
AU  - Yang L
FAU - Du, Fang
AU  - Du F
FAU - Yung, Wing-Ho
AU  - Yung WH
FAU - Ke, Ya
AU  - Ke Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Cation Transport Proteins)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (solute carrier family 11- (proton-coupled divalent metal ion transporters), 
      member 2)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Base Sequence
MH  - Binding Sites
MH  - Cation Transport Proteins/*genetics/metabolism
MH  - Cell Hypoxia/genetics
MH  - Down-Regulation/genetics
MH  - Exons/genetics
MH  - Gene Silencing
MH  - Genetic Vectors/genetics
MH  - Hep G2 Cells
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/metabolism
MH  - Iron/metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Neurons/metabolism
MH  - Protein Binding
MH  - Response Elements/genetics
EDAT- 2010/10/15 06:00
MHDA- 2011/05/17 06:00
CRDT- 2010/10/15 06:00
PHST- 2010/10/15 06:00 [entrez]
PHST- 2010/10/15 06:00 [pubmed]
PHST- 2011/05/17 06:00 [medline]
AID - 10.1002/jcp.22485 [doi]
PST - ppublish
SO  - J Cell Physiol. 2011 Jun;226(6):1596-603. doi: 10.1002/jcp.22485.