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Type: Journal article
Title: Novel DNA binding by a basic helix-loop-helix protein - The role of the dioxin receptor PAS domain
Author: Chapman-Smith, A.
Whitelaw, M.
Citation: Journal of Biological Chemistry, 2006; 281(18):12535-12545
Publisher: Amer Soc Biochemistry Molecular Biology Inc
Issue Date: 2006
ISSN: 0021-9258
Organisation: Centre for the Molecular Genetics of Development
Abstract: Central issues surrounding the basic helix-loop-helix (bHLH) superfamily of dimeric transcription factors concern how specificity of partner selection and DNA binding are achieved. bHLH proteins bind DNA through the basic sequence that is contiguous with a helix-loop-helix dimerization domain. For the two subgroups within the family, dimerization is further regulated by an adjacent Per-Arnt-Sim homology (PAS) or leucine zipper (LZ) domain. We provide evidence that for the bHLH·PAS transcription factors Dioxin Receptor (DR) and Arnt, the DR PAS A domain has a unique interaction with the bHLH region that underpins both dimerization strength and affinity for an atypical E-box DNA sequence. A PAS swap heterodimer, where the DR bHLH domain was fused to Arnt PAS A and the Arnt bHLH fused to DR PAS A, gave strong DNA binding, but dimerization was only effective with the native arrangement, suggesting the PAS A domain is critical for each process via distinct mechanisms. LZ domains, which regulate heterodimerization for the bHLH·LZ family members Myc and Max, could not replace the PAS domains for either dimerization or DNA binding in the DR/Arnt heterodimer. In vitro footprinting revealed that the PAS domains influence the conformation of target DNA in a manner consistent with DNA bending. These results provide the first insights for understanding mechanisms of selective dimerization and DNA interaction that distinguish bHLH·PAS proteins from the broader bHLH superfamily.
Keywords: Animals
Proto-Oncogene Proteins c-myc
Receptors, Aryl Hydrocarbon
Amino Acid Sequence
Base Sequence
Sequence Homology, Amino Acid
Molecular Sequence Data
Basic-Leucine Zipper Transcription Factors
Aryl Hydrocarbon Receptor Nuclear Translocator
Description: © 2006 by The American Society for Biochemistry and Molecular Biology
DOI: 10.1074/jbc.M512145200
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Centre for the Molecular Genetics of Development publications
Molecular and Biomedical Science publications

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