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 in a large family of eukaryotic transcriptional regulatory proteins, such as Sp1. 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 Sp1. 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.
Reddy
G R
GR
Department of Biology and Life Sciences, Savannah State University, GA 31404, USA.
Zawia
N H
NH
D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003080:Cold Temperature; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051766:Early Growth Response Protein 1; D005260:Female; D017874:Immediate-Early Proteins; D007854:Lead / Q000633:toxicity*; D007855:Lead Poisoning / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D020318:Rats, Long-Evans; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers / Q000502:physiology
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D014157:Transcription Factors; D007854:Lead; D004247:DNA