A Neuronal Activity-Dependent Dual Function Chromatin-Modifying Complex Regulates Arc Expression

ABSTRACT: Chromatin modification is an important epigenetic mechanism underlying neuroplasticity. Histone methylation and acetylation have both been shown to modulate gene expression, but the machinery responsible for mediating these changes in neurons has remained elusive. Here we identify a chromatin-modifying complex containing the histone demethylase PHF8 and the acetyltransferase TIP60 as a key regulator of the activity-induced expression of Arc, an important mediator of synaptic plasticity. Clinically, mutations in PHF8 cause X-linked mental retardation while TIP60 has been implicated in the pathogenesis of Alzheimer's disease. Within minutes of increased synaptic activity, this dual function complex is rapidly recruited to the Arc promoter, where it specifically counteracts the transcriptiona

SUBMITTER: Oey NE 

PROVIDER: S-EPMC4586916 | biostudies-literature | 2015 Jan-Feb

REPOSITORIES: biostudies-literature