Neuregulin-1 regulates expression of the Ets-2 transcription factor

At the neuromuscular synapse, synapse-specific gene expression is regulated by neuregulin, a motor neuron-derived factor, and involves participation of the muscle Ets transcription factors. However, the molecular mechanisms regulating expression and activity of the Ets transcription factors at the neuromuscular synapse are largely unknown. This study provides evidence that neuregulin induces expression of the skeletal muscle Ets-2 transcription factor. Recombinant neuregulin (neuregulin-1) induced RNA and protein expression of the Ets-2 transcription factor in L6 myotube cultures. Gene transfer experiments indicated that this neuregulin-elicited increase in Ets-2 expression resulted from enhanced transcription of the Ets-2 gene. Interestingly, electrophoretic mobility shift assays revealed binding activity of the Ets-2 protein to the previously identified neuregulin-response element of the synapse-specific nicotinic acetylcholine receptor epsilon-subunit gene. Taken together, these results identify skeletal muscle Ets-2 transcription factor as a novel target for neuregulin-dependent gene regulation, and suggest a role for this regulation in contributing to motor neuron-dependent control on synapse-specific gene expression at the neuromuscular synapse.