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ARNT2 Tunes Activity-Dependent Gene Expression through NCoR2-Mediated Repression and NPAS4-Mediated Activation
Nikhil Sharma1, Elizabeth A Pollina1, M Aurel Nagy1
1Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Neuron
|March 9, 2019
Summary
The transcription factor ARNT2 regulates neuronal gene expression by interacting with NPAS4. This interaction controls somatic inhibition, ensuring neurons remain receptive to stimuli and scale inhibition with circuit activity.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neuronal activity-dependent transcription is crucial for neural circuit function.
- Aberrant gene induction can disrupt neuronal physiology, but its consequences are unclear.
Purpose of the Study:
- To investigate the role of ARNT2 in regulating activity-dependent gene expression in neurons.
- To elucidate the mechanism by which ARNT2 controls somatic inhibition and neuronal responsiveness.
Main Methods:
- Studied the interaction between ARNT2, NPAS4, and the NCoR2 co-repressor complex.
- Investigated the effects of these interactions on activity-dependent regulatory elements.
- Assessed the impact on gene induction and neuronal inhibition.
Main Results:
- ARNT2, with NCoR2, suppresses inducible genes in the absence of synaptic excitation, maintaining neuronal receptivity.
- ARNT2 recruits NPAS4 during heightened activity to induce transcription and increase somatic inhibition.
- The interplay of bHLH-PAS complexes ensures temporal control of gene expression and scales inhibition with circuit activity.
Conclusions:
- ARNT2 and NPAS4 form a regulatory complex that controls activity-dependent gene expression in neurons.
- This mechanism is vital for balancing neuronal inhibition and excitation, maintaining circuit homeostasis and responsiveness to sensory stimuli.
Keywords:
ARNT2NCoR2NPAS4activity-dependent transcriptionenhancergenomicsinhibitory circuitrepressiontranscriptional regulationMore Related Videos
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