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DNA bending determines Fos–Jun heterodimer orientation

Abstract

Heterodimeric transcription factors can bind to palindromic recognition elements in two opposite orientations with potentially distinct effects on transcriptional activity. We have determined the orientation of Fos–Jun binding at different AP-1 sites using a novel gel-based fluorescence resonance energy transfer assay. The orientation preference of heterodimer binding varied over a greater than 10-fold range. Single base pair substitutions that alter bending of flanking sequences reversed the orientation of heterodimer binding. Single amino acid substitutions that reduce the difference in DNA bending between Fos and Jun also reduced the orientation preference. Consequently, indirect read-out mediated by differences in DNA structure can contribute to the structural organization of nucleoprotein complexes.

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Figure 1: Determination of heterodimer orientation by fluorescence resonance energy transfer.
Figure 2: Orientation of heterodimer binding at AP-1 sites that differ in the bending propensities of flanking sequences.
Figure 3: Influence of flanking sequences on the orientation of heterodimer binding to AP-1 sites containing central C:G or G:C base-pairs.
Figure 4: The influence of differences in DNA bending by Fos and Jun on the orientation of heterodimer binding.

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Correspondence to Tom K. Kerppola.

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Leonard, D., Kerppola, T. DNA bending determines Fos–Jun heterodimer orientation . Nat Struct Mol Biol 5, 877–881 (1998). https://doi.org/10.1038/2316

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