1: Drug Metab Rev. 2001 Feb;33(1):37-47. 

Competitive inhibition of the transcription of rabbit CYP1A1 gene by upstream
stimulatory factor 1 (USF1).

Takahashi Y, Kamataki T.

Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences,
Hokkaido University, Sapporo, Japan.

The induction of CYP1A1 by 3-methylcholanthrene occurs in neonatal but not in
adult rabbits. The expression of aryl hydrocarbon receptor (AhR) and AhR nuclear
translocator (Arnt) mRNAs is seen even in adult rabbits. The CYP1A1 inducibility
does not seem to be regulated by DNA methylation, known to inhibit the
transcription of a gene(s). Preliminary experiments suggest that a constitutive
factor(s) in adult liver nuclear extracts is bound to the core sequence of
rabbit xenobiotic-responsive element (XRE). The sequence of rabbit XRE overlaps
with that of the upstream stimulatory factor 1 (USF1)-binding site. The
AhR/Arnt-mediated activation of XRE-TK/Luc reporter gene in RK13 cells is
blocked by transfection with a USF1 expression vector. These results indicate
that the XRE of the rabbit CYP1A1 gene is recognized by the basic
helix-loop-helix proteins to regulate the expression of CYP1A1 in both an
agonistic (AhR/Arnt) and an antagonistic (USF1) manner.

Publication Types:
    Review
    Review, Tutorial

PMID: 11270661 [PubMed - indexed for MEDLINE]


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2: J Biol Chem. 1997 Nov 28;272(48):30025-31. 

Inhibition of the transcription of CYP1A1 gene by the upstream stimulatory
factor 1 in rabbits. Competitive binding of USF1 with AhR.Arnt complex.

Takahashi Y, Nakayama K, Itoh S, Fujii-Kuriyama Y, Kamataki T.

Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido
University, N12W6, Kita-ku, Sapporo, Hokkaido 060, Japan.
kamataki@pharm.hokudai.ac.jp

A xenobiotic-responsive element (XRE)-binding factor(s) other than the AhR.Arnt
complex was found to inhibit the transcription of CYP1A1 gene in the liver from
adult rabbits, known to be nonresponsive to CYP1A1 inducers. The constitutive
factor(s) in liver nuclear extracts bound to the core sequence of XRE. The
binding was eliminated by the presence of an excess amount of the AhR.Arnt
complex synthesized in vitro. To identify the constitutive factor(s), a sequence
similar to rabbit XRE was sought. It was found that the sequence of rabbit XRE
overlapped with that of the upstream stimulatory factor 1 (USF1)-binding site in
the mouse metallothionein I promoter. In fact, a super shift assay using a
specific antibody against human USF1 indicated that USF1 was capable of binding
to rabbit XRE. Additionally, the AhR.Arnt-mediated activation of XRE-TK/Luc
reporter gene in RK13 cells was blocked by the transfection with a USF1
expression vector with the amounts of the expression vector transfected. These
results indicate that the XRE of the rabbit CYP1A1 gene is recognized by the
basic helix-loop-helix proteins to regulate the expression of CYP1A1 in both an
agonistic (AhR.Arnt) and an antagonistic (USF1) manner.

PMID: 9374477 [PubMed - indexed for MEDLINE]


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3: Biochem Biophys Res Commun. 1997 Nov 17;240(2):293-7. 

Upstream stimulatory factor 1 (USF1) suppresses induction of CYP1A1 mRNA by
3-methylcholanthrene (MC) in HepG2 cells.

Takahashi Y, Nakayama K, Itoh S, Kamataki T.

Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido
University, Japan.

In this study, an endogenous factor(s) involved in the suppression of the
induction of CYP1A1 was studied. Analyzing the sequences, we found that the
sequence of xenobiotic responsive element (XRE) in the upstream region of the
human CYP1A1 gene was overlapped with that of the upstream stimulatory factor 1
(USF1)-binding site in mouse metallothionein I promoter. In fact, a gel shift
assay using a specific competitor or mutant probes showed that the core sequence
of human XRE was specifically recognized by USF1. The amount of USF1 in the
nuclear extracts from HepG2 cells was smaller than that from rat and rabbit
livers as assayed by the binding to XRE. To determine whether or not USF1 could
inhibit the interaction of aryl hydrocarbon receptor (AhR)/AhR nuclear
translocator (Arnt) complex with XRE, we transfected USF1-SR alpha expression
vector into HepG2 cells. The results showed that no interaction of AhR/Arnt
complex with XRE occurred even when the cells were treated with
2,3,7,8-tetrachlorodibenzofuran (TCDF). Furthermore, the S1 nuclease protection
assay showed that the induction of CYP1A1 mRNA by 3-methylcholanthrene (MC) was
depressed by the transfection of USF1-SR alpha into HepG2 cells. Thus, it is
highly possible that USF1 negatively regulates the induction of CYP1A1 in
humans.

PMID: 9388470 [PubMed - indexed for MEDLINE]


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