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Role of the GATA Family of Transcription Factors in Endocrine Development, Function, and Disease

Ontogeny-Reproduction Research Unit (R.S.V., S.M.G.), CHUQ Research Centre, Quebec City, Canada G1V 4G2; Centre de Recherche en Biologie de la Reproduction (R.S.V.), Department of Obstetrics and Gynecology, Faculty of Medicine, Université Laval, Quebec City, Canada G1V 0A6; Department of Obstetrics and Gynecology and Women’s Health Research Program (M.A.) and Children’s Hospital and Women’s Health Research Program (M.H.), Biomedicum Helsinki, University of Helsinki, FI-00014 Helsinki, Finland; and Department of Pediatrics (D.B.W., M.H.), Washington University and St. Louis Children’s Hospital, St. Louis, Missouri 63110

Address all correspondence and requests for reprints to: Robert S. Viger, Ph.D., Ontogeny-Reproduction, Room T1-49, CHUQ Research Centre, 2705 Laurier Boulevard, Quebec City, Quebec, Canada G1V 4G2. E-mail: robert.viger{at}crchul.ulaval.ca; or Markku Heikinheimo, M.D., Ph.D., Children’s Hospital, P.O. Box 22, 00014, University of Helsinki, Helsinki, Finland. E-mail: markku.heikinheimo{at}helsinki.fi.

The WGATAR motif is a common nucleotide sequence found in the transcriptional regulatory regions of numerous genes. In vertebrates, these motifs are bound by one of six factors (GATA1 to GATA6) that constitute the GATA family of transcriptional regulatory proteins. Although originally considered for their roles in hematopoietic cells and the heart, GATA factors are now known to be expressed in a wide variety of tissues where they act as critical regulators of cell-specific gene expression. This includes multiple endocrine organs such as the pituitary, pancreas, adrenals, and especially the gonads. Insights into the functional roles played by GATA factors in adult organ systems have been hampered by the early embryonic lethality associated with the different Gata-null mice. This is now being overcome with the generation of tissue-specific knockout models and other knockdown strategies. These approaches, together with the increasing number of human GATA-related pathologies have greatly broadened the scope of GATA-dependent genes and, importantly, have shown that GATA action is not necessarily limited to early development. This has been particularly evident in endocrine organs where GATA factors appear to contribute to the transcription of multiple hormone-encoding genes. This review provides an overview of the GATA family of transcription factors as they relate to endocrine function and disease.