Genetic variations within the ERE motif modulate plasticity and energetics of binding of DNA to the ERα nuclear receptor.

ABSTRACT: Upon binding to estrogens, the ERα nuclear receptor acts as a transcription factor and mediates a multitude of cellular functions central to health and disease. Herein, using isothermal titration calorimetry (ITC) and circular dichroism (CD) in conjunction with molecular modeling (MM), we analyze the effect of symmetric introduction of single nucleotide variations within each half-site of the estrogen response element (ERE) on the binding of ERα nuclear receptor. Our data reveal that ERα exudes remarkable tolerance and binds to all genetic variants in the physiologically relevant nanomolar-micromolar range with the consensus ERE motif affording the highest affinity. We provide rationale for how genetic variations within the ERE motif may reduce its affinity for ERα by orders of magnitude a

SUBMITTER: Deegan BJ 

PROVIDER: S-EPMC3044919 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature