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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

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 in GABA are reflected by corresponding changes in ( ) expression lev...

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Published in:The Journal of neuroscience 2017-05, Vol.37 (18), p.4778-4789
Main Authors: Wang, Meng, Cai, Elizabeth, Fujiwara, Nana, Fones, Lilah, Brown, Elizabeth, Yanagawa, Yuchio, Cave, John W
Format: Article
Language:English
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Summary: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 in GABA are reflected by corresponding changes in ( ) expression levels. Mechanisms regulating promoter activity are poorly understood, but here we show that a conserved G:C-rich region in the mouse proximal promoter region both recruits heterogeneous nuclear ribonucleoproteins (hnRNPs) that facilitate transcription and forms single-stranded DNA secondary structures associated with transcriptional repression. This promoter architecture and function is shared with ( ), which is also modulated by odorant-dependent activity in the olfactory bulb. This study shows that the balance between DNA secondary structure formation and hnRNP binding on the mouse and promoters in the olfactory bulb is responsive to changes in odorant-dependent sensory input. These findings reveal that and share a novel transcription regulatory mechanism that facilitates sensory input-dependent regulation of dopamine and GABA expression. Adaptation of neural circuits to changes in sensory input can modify several cellular processes within neurons, including neurotransmitter biosynthesis levels. This study shows that transcription of genes encoding rate-limiting enzymes for GABA and dopamine biosynthesis ( and , respectively) in the mammalian olfactory bulb is regulated by G:C-rich regions that both recruit heterogeneous nuclear ribonucleoproteins (hnRNPs) to facilitate transcription and form single-stranded DNA secondary structures associated with repression. hnRNP binding and formation of DNA secondary structure on the and promoters are mutually exclusive, and odorant sensory input levels regulate the balance between these regulatory features. These findings reveal that and share a transcription regulatory mechanism that facilitates odorant-dependent regulation of dopamine and GABA expression levels.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.1363-16.2017