Understanding the effect of tau protein phosphorylation on nucleosome array compaction.

Abstract

Tau is an intrinsically disordered, microtubule associated protein that is mainly expressed in neurons and responsible for stabilizing microtubules in axons. The hyperphosphorylation of tau causes it to dissociate from microtubules which promotes its aggregation into neurofibrillary tangles (NFTs). This can significantly affect brain function. Tau is also found in the nucleus and plays an important role in DNA protection, chromosome stability, and heterochromatin regulation. Recent work has found a correlation between disease-relevant mutations of tau with heterochromatin relaxation, destabilization, and aberrant gene expression. Understanding how tau interacts with nucleosome arrays would give us insight into tau's role in gene expression and regulation. Here, we investigate the question of how the concentration and phosphorylation state of tau affects interactions with nucleosome arrays and their compaction state? We explored this question by using micrococcal nuclease digestion assays to determine the extent of tau's protection on nucleosome arrays. We found that an increase in wild type tau concentration leads to a dramatic increase in array protection but phosphorylated tau shows less dramatic protection patterns. These results provide insights into how tau might be involved in DNA protection and how this process might be disrupted in disease.