RNA sequencing of Tau overexpressing human SH-SY5Y cell line revels that Tau protein is able to alter global gene expression and chromatin structure

Alzheimer’s disease and tauopathies are neurodegenerative disorders characterized by the alteration of neuronal homeostasis and aggregation of Tau protein. Tau is generally considered a protein involved in cytoskeletal stability and transport whose destabilization leads to neuronal dysfunction and death. Despite the knowledge about canonical roles of Tau, in recent years it has been observed that Tau is a key player in several neuronal functions. We previously described that Tau destabilization and nuclear delocalization alters the expression of glutamatergic genes mediating early neuronal damage. In this paper we propose that Tau is able to deeply affect the neuronal transcriptome and that its availability is associated to gene expression alterations occurring in developing intermediate AD phases. In addition, we identify the epigenetic pathway as strongly altered by Tau during AD progression. Differential gene expression analysis of RNA-seq data performed on SH-SY5Y cells overexpressing Tau 0N4R isoform (SH_tau) or a control vector (SH_ctrl). 6 samples in total: 3 samples SH-SY5Y overexpressing Tau 0N4R; 3 samples SH-SY5Y expressing control vector.