GATA factors in endocrine neoplasia

Abstract

GATA transcription factors are structurally-related zinc finger proteins that recognize the consensus DNA sequence WGATAA (the GATA motif), an essential cis-acting element in the promoters and enhancers of many genes. These transcription factors regulate cell fate specification and differentiation in a wide array of tissues. As demonstrated by genetic analyses of mice and humans, GATA factors play pivotal roles in the development, homeostasis, and function of several endocrine organs including the adrenal cortex, ovary, pancreas, parathyroid, pituitary, and testis. Additionally, GATA factors have been shown to be mutated, overexpressed, or underexpressed in a variety of endocrine tumors (e.g., adrenocortical neoplasms, parathyroid tumors, pituitary adenomas, and sex cord stromal tumors). Emerging evidence suggests that GATA factors play a direct role in the initiation, proliferation, or propagation of certain endocrine tumors via modulation of key developmental signaling pathways implicated in oncogenesis, such as the WNT/β-catenin and TGFβ pathways. Altered expression or function of GATA factors can also affect the metabolism, ploidy, and invasiveness of tumor cells. This article provides an overview of the role of GATA factors in endocrine neoplasms. Relevant animal models are highlighted.

The Ovulatory Signal Precipitates LRH-1 Transcriptional Switching Mediated by Differential Chromatin Accessibility

“…Interestingly, our predictive transcription factor binding motif analysis before the OvS revealed the enrichment in GATA factors associated with the LRH-1 motif in open chromatin domains and LRH-1 binding regions. GATA transcription factors play important roles in cellular reprogramming to regulate cell fate specification and differentiation (Iwafuchi-Doi and Zaret, 2014;Pihlajoki et al, 2016). For instance, GATA transcription factors have been shown to cooperate as pioneer factors with other nuclear receptors, such as AR and ERa, to initiate specific transcriptional programs (Zaret and Carroll, 2011).…”

Probing GATA factor function in mouse Leydig cells via testicular injection of adenoviral vectors

“…This finding is reminiscent of a study in which treatment of MA-10 cells with an apoptosis-inducing agent caused a decrease in steroid production in advance of cell death (King et al 1998). GATA4 has been shown to enhance cell survival and/or decrease apoptosis in Leydig cell lines and other steroidogenic cell types (Bennett et al 2013, Anttonen et al 2014, Schrade et al 2015, Pihlajoki et al 2016). The precise mechanism of cell death in our model remains unclear.…”

Novel roles for GATAe in growth, maintenance and proliferation of cell populations in the Drosophila renal tubule

“…The GATA family of transcription factors (TFs) contain one or two zinc-finger domains that bind to the consensus DNA sequence A/T GATA A/G and is known to play crucial roles in the development and physiology of vertebrates, invertebrates, plants and fungi (Lentjes et al, 2016;Merika and Orkin, 1993). Aside from their developmental roles, vertebrate GATA factors are associated to diverse types of cancers, including intestinal tumors, leukemia, and breast cancer (Zheng and Blobel, 2010;Pihlajoki et al, 2016;Hellebrekers et al, 2009;Shaoxian et al, 2017). In humans, at least two GATA factors are expressed in the kidney (GATA3 and GATA5).…”