GATA factors: Master regulators of gene expression in trophoblast progenitors

Abstract

Mammalian reproduction is critically dependent on trophoblast cells, which ensure embryo implantation and placentation. Development of trophoblast cell lineages is a multi-step process and relies upon proper spatial and temporal gene expression, which is regulated by multiple transcription factors. However, most of the transcription factors that are implicated in trophoblast development regulate gene expression at a specific developmental stage or in a specific trophoblast subtype. In contrast, recent studies from our group and other laboratories indicate that conserved GATA family of transcription factors, GATA2 and GATA3, are important to regulate gene expression at multiple stages of trophoblast development. Furthermore, our conditional gene deletion studies revealed that functional redundancy of GATA2 and GATA3 ensures both self-renewal of trophoblast stem and progenitor cells and their differentiation to trophoblast cells of a matured placenta. Together these findings indicate that GATA2/GATA3 are the master orchestrators of gene expression in trophoblast cells and they fine tune gene regulatory network to establish distinct trophoblast cell types during placentation.

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

“…Our CpGs were also enriched for genes regulated by specific transcription factors, most notably GATA1 and GATA2. Together with PPARG and TP63, GATA factors are part of the core transcriptional regulatory circuit that guides and maintains proper trophoblast differentiation 45,46 . Placentas lacking PPARG have lethal defects in placental vascularisation 43 , and angiogenic activity is reduced in placentas lacking GATA2 47 .…”

GATA3 as a master regulator and therapeutic target in ovarian high‐grade serous carcinoma stem cells

“…In hematopoiesis, GATA3 is involved in the earliest steps of Tcell development in the thymus, 23 and is expressed exclusively in quiescent long-term hematopoietic stem cells that are responsible for long-term, lineagespecific repopulation. 27 In fibroblasts, OCT4 can be replaced by GATA3 to reprogram both human and mouse fibroblasts to induced pluripotent stem cells (iPSCs). 25 In neural progenitor cells, GATA3 is induced after injury, and is required for regenerative neurogenesis, 26 and ensures self-renewal in both human and mouse trophoblastic stem cells.…”

“…25 In neural progenitor cells, GATA3 is induced after injury, and is required for regenerative neurogenesis, 26 and ensures self-renewal in both human and mouse trophoblastic stem cells. 27 In fibroblasts, OCT4 can be replaced by GATA3 to reprogram both human and mouse fibroblasts to induced pluripotent stem cells (iPSCs). 28,29 Together, all these studies suggest a stemness role for GATA3 in developmental biology.…”

Liganded T3 receptor β2 inhibits the positive feedback autoregulation of the gene for GATA2, a transcription factor critical for thyrotropin production

“…Thus, the precise mechanism of the effect of T3 on the GATA2-related hematopoiesis should be investigated in future. Current results also predict that serum TSH level may be correlated with placental function because this organ expresses GATA family members [32,33] as well as TRs [86]. As is the case with the TSHβ and CGA gene in the pituitary (Fig 7), GATA2 and GATA3 regulate the expression of the genes that encode the critical proteins responsible for maintaining the placental function, including the component of bone morphogenetic protein 4, Nodal and Wnt signals [32].…”

“…Although numerous mathematical models [26-28] and the involvement of genetic factors [29] have been proposed, there are few experimental systems that enable us to explore the molecular mechanism underlying this unique relationship between them. GATA2 is expressed not only in thyrotroph but also in gonadotroph [2,3,30] and placenta [31][32][33], resulting in the potentiation of the CGA gene expression [34,35]. Using trophoblast stem cell line, Rcho-1, and TS cells, Ray et al [36] surveyed approximately 100-kb regions of the rat and mouse GATA loci using quantitative chromatin immunoprecipitation (ChIP) assay.…”