Genetic Anatomy and Ontogenetic Roles of Early Growth Response 1 (Egr1) in Human and Mouse

The early growth response 1 (Egr1) gene is a well-known immediate-early gene in the Egr family. It encodes cysteine-2-histidine-2 (C2H2)-type zinc-finger DNA binding domain. EGR1 is involved in various developmental processes, including cell proliferation, differentiation, inflammation, neuroplasticity, angiogenesis, and endocrine. Egr1 deficiency causes infertility due to impaired ovulation associated with the non-expression of LHβ. It has also been suggested that EGR1 may be essential for endometrial differentiation. Interestingly, EGR1 suppresses or activates the expression of downstream genes, depending on the cellular environment and stimuli. This is suspected to be influenced by the level of EGR1, its structure, and its interactions with other transcription regulators. Egr1 gene is constructed with 2 exons and 1 intron without alternative spliced transcripts in both human and mouse. Egr1 expression is under the control of itself and other cis- and trans-factors. Egr1 has one promoter and a few enhancers with differences between human and mouse. The promoter contains binding sites for various transcription factors, including EGR1, activator protein 1 (AP1), EGR1 binding site (EBS), and specificity protein 1 (SP1). TATA and CAT boxes are present in the mouse Egr1 gene, but the TATA box is found only in humans. EGR1 is also suggested as a target for treatment for some diseases, like cancer, but it requires much more basic knowledge. Understanding EGR1's cell type-specific functions at the various levels will be helpful in understanding the normal development and in finding therapeutic targets in reproduction, cancer, and immune-related diseases. In this review, we briefly summarize the genetic anatomy with the molecular and developmental roles of EGR1.