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

Zinc finger proteins (ZFP) contain a structural motif (Cys-2 His-2) found i n a large family of eukaryotic transcriptional regulatory proteins, such as Spl. Previous studies have shown that Spl DNA-binding was disrupted by exp osure 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 di fferentiation. Egr-1 DNA-binding was studied by gel shift mobility assays i n several brain regions of developing rat pups. We observed a distinct deve lopmental profile of Egr-1 DNA-binding with a gradual increase from the ear ly to late postnatal days in all the brain regions examined. Lactational ex posure to Pb resulted in a modulation of Egr-1 DNA binding manifested by pr emature peaks in DNA-binding reminiscent of the in vivo changes previously reported for Spl. These data are consistent with earlier findings that expo sure to Pb both in vivo and in vitro causes a modulation ill the DNA-bindin g of ZFP such as Spl, Egr-1 and TFIIIA. The commonality by which Pb exposur e alters the DNA-binding patterns of ZFP suggests that divalent Pb may be i nteracting directly with the Zn moiety of these proteins. (C) 2000 ISDN. Pu blished by Elsevier Science Ltd. All rights reserved.