Presenter of 1 Presentation
A TAU-DEPENDENT MECHANISM OF EPIGENETIC MODULATION OF GENE EXPRESSION
Abstract
Aims
Explain the molecular mechanism of Tau-dependent epigenetic modification associated to neurodegeneration and causing heterochromatin loss in disease.
Methods
RNA-seq, Western Blot, Immunofluorescence Microscopy, Co-immunoprecipitation, qPCR, SA-βgalactosidase assay, FACS
Results
We discovered that a loss-of-function of Tau affects cell fate ultimately promoting a senescent state (Magrin et al, Commun Biol 3:245. 2020). We now report the outcome of an RNAseq analysis and the identification of a small set of genes up-regulated in Tau-KO cells when compared to parental, Tau-expressing cells. Bioinformatical analysis of their promotor regions points to a shared epigenetic mechanism of regulation. We also report a cell pathway implicated in the Tau-dependent induction of cellular senescence, a process implicated in neurodegeneration and cognitive decline in a tauopathy mouse model.
Conclusions
This new Tau function may provide a mechanism explaining heterochromatin loss in disease and advance our understanding of the molecular process leading to neurodegeneration.