title: GATA factors are essential for activity of the neuron-specific enhancer of the gonadotropin-releasing hormone gene.
abstract: The multicomponent neuron-specific enhancer of the gonadotropin-releasing hormone (GnRH) gene specifically targets expression to the GnRH-secreting 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 transcription 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 GATA-4 was detected in a GnRH enhancer GATA site-specific complex. Cotransfection experiments with wild-type and mutant GnRH enhancer reporter plasmids with wild-type and dominant negative GATA factor expression vectors demonstrated that both GATA-binding elements are functional in the 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 cells is novel for a neuronal cell type. However, the presence of GATA-4 is 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.
authors.affiliation: Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093-0674, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Lawson
authors.forename: D B
authors.initials: DB
authors.lastname: Whyte
authors.forename: P L
authors.initials: PL
authors.lastname: Mellon
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D050989:GATA2 Transcription Factor; D050991:GATA4 Transcription Factor; D007987:Gonadotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics*; D007031:Hypothalamus / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; D050991:GATA4 Transcription Factor; C494712:Gata2 protein, mouse; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D014157:Transcription Factors; D007987:Gonadotropin-Releasing Hormone; D015500:Chloramphenicol O-Acetyltransferase