Nup153 regulates neuronal responsiveness through HDAC1-mediated epigenetic modulation [ATAC-seq]

Induction of activity-dependent gene programs is equally important as repression of these programs, and both need to be balanced carefully. However, little is known about how repressive mechanisms modulate neuronal responsiveness across the genome before stimulation.

Here, we identify nucleoporin-dependent regulation of neuronal responsiveness in which Nup153 represses neuronal genes including activity-regulated genes (ARGs) in the basal state. By characterizing the genome-wide landscape of chromatin accessibility, histone modifications and Nup153 chromatin binding, we show that Nup153 directly influences their target genes and associated chromatin states through both basal activity-dependent and -independent mechanisms.