The 25th Volume: Role of the GATA Family of Transcription Factors in Andrology

Abstract

Understanding how genes get turned on or off is central to the study of biological processes in both health and disease. Several regulatory mechanisms, which can be positive or negative, have been implicated in the control of tissue-and cell-specific gene expression. These include modulation of chromatin structure, DNA methylation, and the regulation of transcription and translation. Transcription factors are nuclear regulatory proteins that bind specific DNA sequences in the 5Ј regulatory or promoter regions of target genes. They are involved in both basal and tissue-specific gene expression. There are several classes of transcription factors that have been defined based on similarities in the structure of the respective DNA-binding domains. They include zinc finger, helixloop-helix, leucine zipper, and homeobox transcription factors. The GATA family of zinc finger transcription factors is named from the consensus nucleotide sequence (A/ TGATAA/G) that these factors bind in the promoter regions of target genes. They were originally identified as crucial regulators of heart development and the differentiation of blood and immune cells. GATA expression, however, is not limited to these two systems. Indeed, reproductive tissues such as the testis and ovary are also prominent sites of GATA expression. As few as 5 years ago, the role of GATA factors in reproductive function was uncharted territory. With the recent contributions to the field, the scientific community has come a long way in filling this void. GATA factors have now been impliCorrespondence to: Dr Robert S. Viger, Ontogeny-Reproduction, Room T1-49, CHUL Research Centre, 2705 Laurier Blvd, Ste-Foy, Québec, Canada G1V 4G2 (e-mail: Robert.Viger@crchul.ulaval.ca).Received for publication January 29, 2004; accepted for publication February 4, 2004. cated in gonadal development, male sex determination and differentiation, and steroidogenesis. This review will provide a brief overview of the vertebrate family of GATA factors and how these factors have affected the field of andrology.

GATA Factors and Androgen Receptor Collaborate To Transcriptionally Activate theRhox5Homeobox Gene in Sertoli Cells

“…These are highly conserved zinc finger-containing proteins that are found across the phylogenetic scale where they have conserved roles regulating cell differentiation, organ morphogenesis, and tissue-specific gene expression (32,34,61,62,68). In the reproductive system, GATA4 is essential for mouse gonad development and male sex determination (34,62). While the precise mechanism by which GATA4 drives the indifferent gonad down the male pathway remains to be determined, various GATA4-regulated genes have been identified that are likely to have a role, including the male-determining gene Sry and the male-inhibitory gene Mis (60).…”

“…To test this prediction, we used real-time RT-PCR analysis to examine GATA transcription factor mRNA levels. Sertoli cells are known to express GATA4 and GATA6 (62), and thus we predicted that one or both of these factors would be lower in 15P1 and TM4 cells than in MSC1 cells. Indeed, we found that Gata4 and Gata6 transcripts were expressed at lower levels in 15P1 and TM4 cells than in MSC1 cells (Fig.…”

“…These data are consistent with the possibility that the low expression of one or both of these factors is responsible for limiting Pp expression in 15P1 and TM4 cells. We also examined the expression of Gata1 mRNA, as GATA1 is expressed by Sertoli cells in vivo (62). None of the Sertoli cell lines, including MSC1, had appreciable levels of Gata1 mRNA (less than 0.033% of the level in adult testis) (Fig.…”

“…This well-studied class of zinc-transcription factors has a conserved and important role in embryonic development and activates the transcription of several key transcription factor genes during the formation of gonads (62). GATA factors are also expressed in Sertoli cells in male gonads after birth, leading to widely held notion that they serve to drive spermatogenesis (34,43,62,63). Our finding that GATA factors transcriptionally activate Rhox5 suggests that upregulation of this germ cell survival factor is one means by which GATA factors could promote spermatogenesis.…”

Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice

“…FOG2 is a multitype zinc finger cofactor that binds to and regulates the transcriptional activity of GATA4, a member of the GATA family of transcription factors (22)(23)(24). In mice, Fog2 and Gata4 are coexpressed in the somatic cells of XX and XY genital ridges as early as embryonic day (E) 10.5 (25-28).…”