Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability.
Steven C WylerW Clay SpencerNoah H GreenBenjamin D RoodLaTasha K CrawfordCaryne CraigePaul GreschDouglas G McMahonSheryl G BeckEvan DenerisPublished in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
The regulatory mechanisms that control functional maturation of neurons are poorly understood. We show that in addition to inducing brain serotonin (5-HT) synthesis and reuptake, the Pet-1 ETS (E26 transformation-specific) factor subsequently globally coordinates postmitotic expression trajectories of genes necessary for maturation of 5-HT neuron excitability. Further, Pet-1 switches its transcriptional targets as 5-HT neurons mature from 5-HT synthesis genes to G-protein-coupled receptors, which are necessary for afferent synaptic modulation of 5-HT neuron excitability. Our findings uncover gene-specific switching of downstream targets as a previously unrecognized regulatory strategy through which continuously expressed transcription factors control acquisition of neuronal identity at different stages of development.
Keyphrases
- transcription factor
- genome wide identification
- genome wide
- pet ct
- computed tomography
- positron emission tomography
- transcranial direct current stimulation
- spinal cord
- gene expression
- dna binding
- pet imaging
- depressive symptoms
- genome wide analysis
- dna methylation
- cerebral ischemia
- white matter
- resting state
- bioinformatics analysis
- blood brain barrier
- oxidative stress
- working memory
- brain injury