Retinal neuron activity of ETS domain-binding sites in a nicotinic acetylcholine receptor gene cluster enhancer

Nicotinic acetylcholine receptors (nAchRs) mediate amacrine to ganglion cell synaptic transmission in the developing mammalian retina. The clustered neuronal nAchRs subunit genes, alpha 3 and beta 4, are expressed in amacrine and ganglion cells where they are used to assemble functional receptor subtypes. The transcriptional mechanisms underlying expression of these subunits in retina are not yet known but may involve enhancers that are selectively active in retinal neurons. We previously identified a neuron-selective enhancer, beta 43', whose activity in neural cell lines is dependent on ETS domain-binding sites. To determine whether beta 43' is active in retinal neurons that express the alpha 3 and beta 4 genes, we investigated beta 43' activity in primary dissociated rat retinal cultures. We found that beta 43' is selectively active in retinal neurons compared with retinal non-neuronal cells. This activity was derived primarily from amacrine and ganglion neurons, which are the retinal neuron cell types that express the clustered genes. Moreover, beta 43' was selectively active in retinal neurons compared with cerebral cortical neurons suggesting that it is not a pan-neuronal enhancer. ETS factor-binding sites in the enhancer are required for its retinal neuron activity. These findings suggest that ETS factor interactions with beta 43' control retinal neuron expression of certain nAchR subtypes.