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Mol Cell Biol, July 1998, p. 4079-4088, Vol. 18, No. 7
Department of Cell and Molecular Biology,
Karolinska Institutet, S-171-77 Stockholm, Sweden
Received 1 December 1997/Returned for modification 23 February
1998/Accepted 13 April 1998
The dioxin receptor is a ligand-regulated transcription factor that
mediates signal transduction by dioxin and related environmental pollutants. The receptor belongs to the basic helix-loop-helix (bHLH)-Per-Arnt-Sim (PAS) family of factors, which, in addition to the
bHLH motif, contain a PAS region of homology. Upon activation, the
dioxin receptor dimerizes with the bHLH-PAS factor Arnt, enabling the
receptor to recognize xenobiotic response elements in the vicinity of
target genes. We have studied the role of the PAS domain in
dimerization and DNA binding specificity of the dioxin receptor and
Arnt by monitoring the abilities of the individual bHLH domains and
different bHLH-PAS fragments to dimerize and bind DNA in vitro and
recognize target genes in vivo. The minimal bHLH domain of the
dioxin receptor formed homodimeric complexes, heterodimerized with
full-length Arnt, and together with Arnt was sufficient for recognition
of target DNA in vitro and in vivo. In a similar fashion, only the bHLH
domain of Arnt was necessary for DNA binding specificity in the
presence of the dioxin receptor bHLH domain. Moreover, the bHLH domain
of the dioxin receptor displayed a broad dimerization potential, as
manifested by complex formation with, e.g., the unrelated bHLH-Zip
transcription factor USF. In contrast, a construct spanning the dioxin
receptor bHLH domain and an N-terminal portion of the PAS domain
failed to form homodimers and was capable of dimerizing only with Arnt.
Thus, the PAS domain is essential to confer dimerization specificity of
the dioxin receptor.
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Role of the PAS Domain in Regulation of
Dimerization and DNA Binding Specificity of the Dioxin
Receptor
and
*
Corresponding author. Mailing address: Department of
Cell and Molecular Biology, Karolinska Institutet, S-171-77
Stockholm, Sweden. Phone: 46-8 728 7330. Fax: 46-8 34 88 19. E-mail: Lorenz.Poellinger{at}cmb.ki.se.
Present address: Dept. of Biochemistry, University of Adelaide,
Adelaide 5005, South Australia, Australia.
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