Chapter XII the Egr Transcription Factors and Their Utility in Mapping Brain Functioning

This chapter reviews the structure of the Egr genes and proteins and their DNA binding. The defining feature of the Egr family of proteins is their three zinc finger motifs, which recognize the same nine-base-pair segment of DNA. Once bound to the promoters of target genes, the proteins act in concert with other transcription factors to regulate the expression of these genes. The chapter describes the expression of the Egrs in cell culture and in the brain. In glial cells, all Egrs can be activated via the M1 acetylcholine receptor. Egr-1 binds to the promoters and initiates transcription of the genes for phenylethanolamine N-methyl transferase, neurofilament, synapsin I, synaptophysin I and II, apolipoprotein A1, platelet-derived growth factor B, and nur77, and it represses the adenosine deaminase gene. Additionally, the egr-1 gene contains an estrogen response element (ERE) and is thus itself a target of Egr-1 proteins. Egr-2 regulates some Hox genes to cause peripheral nerve myelination and hindbrain segmentation during development. The JunB and JunD promoters also contain one or more EREs so their activity might be under some control by the Egrs.