The DAXX tax: C9orf72 DNA repeat expansions drive gain- and loss-of-function pathology in c9FTD/ALS

In this issue of Neuron, Liu et al.(1) identify DAXX as a C9orf72 hexanucleotide repeat expansion DNA-binding protein that initiates epigenetic modifications and chromatin remodeling, contributing to C9orf72 haploinsufficiency by inhibiting its stress-inducible expression and mediating both loss-and toxic gain-of-function pathology.

Automated summary

In this study, Liu et al. identified DAXX as a protein that binds to the C9orf72 hexanucleotide repeat expansion DNA. They found that DAXX plays a role in initiating epigenetic modifications and chromatin remodeling, leading to C9orf72 haploinsufficiency, inhibiting its stress-inducible expression, and mediating both loss and toxic gain-of-function pathology.