Lead exposure alters Egr-1 DNA-binding in the neonatal rat brain

Abstract

Zinc finger proteins (ZFP) contain a structural motif (Cys-2 His-2) found in a large family of eukaryotic transcriptional regulatory proteins, such as Spl. Previous studies have shown that Sp1 DNA-binding was disrupted by exposure to lead (Pb), due to action on its zinc finger domain. In this paper, we discuss the results of studies with another ZFP, Egr-1, an early growth response gene, which is functionally involved in cell proliferation and differentiation. Egr-1 DNA-binding was studied by gel shift mobility assays in several brain regions of developing rat pups. We observed a distinct developmental profile of Egr-1 DNA-binding with a gradual increase from the early to late postnatal days in all the brain regions examined. Lactational exposure to Pb resulted in a modulation of Egr-1 DNA binding manifested by premature peaks in DNA-binding reminiscent of the in vivo changes previously reported for Spl. These data are consistent with earlier findings that exposure to Pb both in vivo and in vitro causes a modulation in the DNA-binding of ZFP such as Sp1, Egr-1 and TFIIIA. The commonality by which Pb exposure alters the DNA-binding patterns of ZFP suggests that divalent Pb may be interacting directly with the Zn moiety of these proteins.