GATA FACTORS ARE ESSENTIAL FOR ACTIVITY OF THE NEURON-SPECIFIC ENHANCER OF THE GONADOTROPIN-RELEASING-HORMONE GENE

The multicomponent neuron-specific enhancer of the gonadotropin-releas ing hormone (GnRH) gene specifically targets expression to the GnRH-se creting neurons of the hypothalamus, a small population of specialized cells which play a central role in regulating reproductive function. Utilizing the GnRH-secreting hypothalamic neuronal cell line, GT1, as a model system, we show that members of the GATA family of transcripti on factors regulate GnRH transcription through two GATA factor-binding motifs that occur in a tandem repeat within the GnRH neuron-specific enhancer. Although GT1 cells contain GATA-2 and GATA-4 mRNAs, only GAT A-4 was detected in a GnRH enhancer GATA site-specific complex. Cotran sfection experiments with wildtype and mutant GnRH enhancer reporter p lasmids with wild-type and dominant negative GATA factor expression ve ctors demonstrated that both GATA-binding elements are functional in t he context of the enhancer, We conclude that GATA-binding proteins are important factors in regulating the neuron-specific expression of the GnRH gene in hypothalamic cells, Although the presence of GATA-2 in a neuronal cell type is not unusual, the presence of GATA-4 in GT1 cell s is novel for a neuronal cell type, However, the presence of GATA-4 i s consistent with the unique developmental origin of GnRH neurons and may provide insight into the transcriptional mechanisms mediating the differentiation of this limited population of GnRH-secreting neurons.