Author:
Brigidi G. Stefano,Hayes Michael G. B.,Hartzell Andrea L.,Texari Lorane,Lin Pei-Ann,Bartlett Anna,Ecker Joseph R,Benner Christopher,Heinz Sven,Bloodgood Brenda L.
Abstract
SUMMARYCells regulate gene expression in response to salient external stimuli. In neurons, depolarization leads to the expression of inducible transcription factors (ITFs) that direct subsequent gene regulation. Depolarization encodes both a neuron’s action potential (AP) output and synaptic inputs, via excitatory postsynaptic potentials (EPSPs). However, it is unclear if different types of depolarizing signals can be transformed by an ITF into distinct modes of genomic regulation. Here, we show that APs and EPSPs in the murine hippocampus trigger two spatially segregated and molecularly distinct mechanisms that lead to the expression of the ITF NPAS4. These two pathways culminate in the assembly of unique, stimulus-specific NPAS4 heterodimers that exhibit distinctive DNA binding patterns. Thus, NPAS4 independently communicates increases in a neuron’s spiking output and synaptic inputs to the nucleus, enabling gene regulation to be tailored to the type of depolarizing activity experienced by a neuron.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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