Two classes of androgen receptor elements mediate cooperativity through allosteric interactions
Reid, Kimberly, Hendy, Stephen, Saito, Jody, Sorenson, Pernille, & Nelson, Colleen C. (2001) Two classes of androgen receptor elements mediate cooperativity through allosteric interactions. Journal of Biological Chemistry, 276(4), pp. 2943-2952.
Genes uniquely regulated by the androgen receptor (AR) typically contain multiple androgen response elements (AREs) that in isolation are of low DNA binding affinity and transcriptional activity. However, specific combinations of AREs in their native promoter context result in highly cooperative DNA binding by AR and high levels of transcriptional activation. We demonstrate that the natural androgen-regulated promoters of prostate specific antigen and probasin contain two classes of AREs dictated by their primary nucleotide sequence that function to mediate cooperativity. Class I AR-binding sites display conventional guanine contacts. Class II AR-binding sites have distinctive atypical sequence features and, upon binding to AR, the DNA structure is dramatically altered through allosteric interactions with the receptor. Class II sites stabilize AR binding to adjacent class I sites and result in synergistic transcriptional activity and increased hormone sensitivity. We have determined that the specific nucleotide variation within the AR binding sites dictate differential functions to the receptor. We have identified the role of individual nucleotides within class II sites and predicted consensus sequences for class I and II sites. Our data suggest that this may be a universal mechanism by which AR achieved unique regulation of target genes through complex allosteric interactions dictated by primary binding sequences.
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|Item Type:||Journal Article|
|Additional Information:||Articles free to read on journal website after 12 months|
|Divisions:||Past > QUT Faculties & Divisions > Faculty of Science and Technology|
|Copyright Owner:||Copyright 2001 American Society for Biochemistry and Molecular Biology|
|Deposited On:||19 Oct 2007 00:00|
|Last Modified:||04 Feb 2015 06:08|
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