CUT homeobox factors modulate chromatin accessibility in neurons

ABSTRACT Neuronal identity relies on coordinated transcriptional programs that include both neuron type-specific features and broadly shared pan-neuronal properties. While transcription factors that control neuronal gene expression have been defined, how these regulators interface with chromatin accessibility at neuronal loci remains poorly understood. CUT homeobox factors are broadly expressed in the C. elegans nervous system and provide a genetically defined system to examine transcription factor associated chromatin accessibility in neurons. Here, we establish a fluorescence-activated sorting workflow to enrich neuronal nuclei using a pan-neuronal nuclear marker and apply bulk ATAC-seq to profile chromatin accessibility in wild-type and CUT mutant animals. We identify CUT-dependent accessibility differences in neuronal nuclei, with changes concentrated at promoter-proximal regions and linked to neuronal genes, including neuronally enriched and pan-neuronal categories. Together, this work provides in vivo neuronal chromatin accessibility profiles and defines CUT-dependent changes at a subset of neuronal regulatory regions.