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https://hdl.handle.net/2440/24017
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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 1083-351X |
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 Humans Mice Leucine Proto-Oncogene Proteins c-myc Receptors, Aryl Hydrocarbon DNA 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 |
Published version: | http://www.jbc.org/cgi/content/abstract/281/18/12535 |
Appears in Collections: | Aurora harvest 2 Centre for the Molecular Genetics of Development publications Molecular and Biomedical Science publications |
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