Role of the transcription factor EGR1 in the neuronal survival

Cells respond to neural stimuli through the rapid and transient induction of a set of genes called immediate early genes (IEGs). Among these genes, EGR1 (early growth response gene 1) encodes for a transcription factor known to be involved in different biological functions such as cell growth, differentiation and apoptosis. In the neuronal development, EGR1 has been hypothesized to have a role in differentiation, neuronal plasticity, and in the development of learning and memory. The scope of our study is to evaluate the involvement of EGR1 in the neuronal cell proliferation, survival and death. To this aim, we used SH-SY5Y neuroblastoma cell line and CRISPR-Cas9 technology to generate an EGR1 knock-out (KO) neuronal cell model. EGR1-KO cells show clear morphological differences, and higher proliferation and migration rate compared to WT cells. Under different stress conditions, such as serum withdrawal and H2O2-induced oxidative stress, KO cells have higher survival rate than WT cells. A preliminary molecular analysis demonstrated that KO cells react to stress-induced conditions by triggering autophagy process in contrast to WT cells. Therefore, EGR1 knockout cells may represent an interesting model for studying the molecular mechanisms regulated by EGR1 for the proper development, differentiation and survival of neurons.