Odorant sensory input modulates DNA secondary structure formation and heterogeneous ribonucleoprotein recruitment on the tyrosine hydroxylase and glutamic acid decarboxylase 1 promoters in the olfactory bulb

Abstract

Adaptation of neural circuits to changes in sensory input can modify several cellular processes within neurons, including neurotransmitter biosynthesis levels. For a subset of olfactory bulb interneurons, activity-dependent changes inGABAare reflected by corresponding changes in Glutamate decarboxylase 1 (Gad1) expression levels. Mechanisms regulating Gad1 promoter activity are poorly understood, but here we show that a conserved G:C-rich region in the mouse Gad1 proximal promoter region both recruits heterogeneous nuclear ribonucleoproteins (hn- RNPs) that facilitate transcription and forms single-stranded DNA secondary structures associated with transcriptional repression. This promoterarchitectureandfunction issharedwithTyrosinehydroxylase(Th),whichis alsomodulatedbyodorant-dependentactivity in the olfactory bulb. This study shows that the balance betweenDNAsecondary structure formation andhnRNPbindingonthemouseThandGad1promoters in the olfactory bulb is responsive to changes in odorant-dependent sensory input. These findings reveal that Th and Gad1 share a novel transcription regulatory mechanism that facilitates sensory input-dependent regulation of dopamine and GABA expression.