Development and Carcinogenesis: Roles of GATA Factors in the Sympathoadrenal and Urogenital Systems

The GATA family of transcription factors consists of six proteins (GATA1-6) that control a variety of physiological and pathological processes. In particular, GATA2 and GATA3 are coexpressed in a number of tissues, including in the urogenital and sympathoadrenal systems, in which both factors participate in the developmental process and tissue maintenance. Furthermore, accumulating studies have demonstrated that GATA2 and GATA3 are involved in distinct types of inherited diseases as well as carcinogenesis in diverse tissues. This review summarizes our current knowledge of how GATA2 and GATA3 participate in the transcriptional regulatory circuitry during the development of the sympathoadrenal and urogenital systems, and how their dysregulation results in the carcinogenesis of neuroblastoma, renal urothelial, and gynecologic cancers.

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

Molecular Endocrinology ◽

10.1210/me.2007-0513 ◽

2008 ◽

Vol 22 (4) ◽

pp. 781-798 ◽

Cited By ~ 160

Author(s):

Robert S Viger ◽

Séverine Mazaud Guittot ◽

Mikko Anttonen ◽

David B Wilson ◽

Markku Heikinheimo

Keyword(s):

Transcription Factors ◽

Endocrine Function ◽

Specific Gene ◽

Functional Roles ◽

Gata Factors ◽

Early Embryonic Lethality ◽

Transcriptional Regulatory ◽

Organ Systems ◽

Endocrine Organs ◽

Gata Family

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.

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A Drosophila GATA family member that binds to Adh regulatory sequences is expressed in the developing fat body

Development ◽

10.1242/dev.119.3.623 ◽

1993 ◽

Vol 119 (3) ◽

pp. 623-633 ◽

Cited By ~ 13

Author(s):

T. Abel ◽

A.M. Michelson ◽

T. Maniatis

Keyword(s):

Fat Body ◽

Regulatory Elements ◽

Drosophila Embryo ◽

Cdna Clones ◽

Regulatory Sequences ◽

Mammalian Development ◽

Sequence Element ◽

Gata Factors ◽

Transcriptional Regulatory ◽

Gata Family

We have identified a Drosophila transcription factor that binds a sequence element found in the larval promoters of all known alcohol dehydrogenase (Adh) genes. DNA sequence analysis of cDNA clones encoding this protein, box A-binding factor (ABF), reveals that it is a member of the GATA family of transcriptional regulatory factors. ABF-binding sites within the D. mulleri and D. melanogaster larval Adh promoters function as positive regulatory elements and in cotransfection experiments, ABF functions as a transcriptional activator. In further support of a role for ABF in the regulation of Adh expression, ABF mRNA is expressed in the embryonic fat body, a tissue that contains high levels of Adh mRNA. Our studies demonstrate that the fat body develops from segmentally repeated clusters of mesodermal cells, which later expand and coalesce to form the mature fat body. These observations establish ABF as the earliest known fat body precursor marker in the Drosophila embryo. Together with the established role of GATA factors during mammalian development, these results suggest that ABF may play a key role in the organogenesis of the fat body.

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Regulation of the ANF and BNP promoters by GATA factors: Lessons learned for cardiac transcription

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y01-037 ◽

2001 ◽

Vol 79 (8) ◽

pp. 673-681 ◽

Cited By ~ 35

Author(s):

Kevin McBride ◽

Mona Nemer

Keyword(s):

Transcription Factors ◽

Natriuretic Peptide ◽

Regulatory Networks ◽

Current Knowledge ◽

Lessons Learned ◽

Clinical Markers ◽

Gata Factors ◽

Major Mechanism ◽

Genes Encoding ◽

Cardiac Gene

The identification and molecular cloning of the cardiac transcription factors GATA-4, -5, and -6 has greatly contributed to our understanding of how tissue-specific transcription is achieved during cardiac growth and development. Through analysis of their interacting partners, it has also become apparent that a major mechanism underlying spatial and temporal specificity within the heart as well as in the response to cardiogenic regulators is the combinatorial interaction between cardiac-restricted and inducible transcription factors. The cardiac GATA factors appear to be fundamental contributors to these regulatory networks. Two of the first targets identified for the cardiac GATA factors were the natriuretic peptide genes encoding atrial natriuretic factor (ANF) and B-type natriuretic peptide (BNP), the major heart secretory products that are also accepted clinical markers of the diseased heart. Studies using the ANF and BNP promoters as models of cardiac-specific transcription have unraveled the pivotal role that GATA proteins play in cardiac gene expression. We review the current knowledge on the modulation of the natriuretic peptide promoters by GATA factors, including examples of combinatorial interactions between GATA proteins and diverse transcription factors.Key words: ANF, BNP, GATA factors, cardiac transcription.

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Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression

Biochemistry and Cell Biology ◽

10.1139/o05-062 ◽

2005 ◽

Vol 83 (4) ◽

pp. 535-547 ◽

Cited By ~ 7

Author(s):

Gareth N Corry ◽

D Alan Underhill

Keyword(s):

Gene Expression ◽

Transcription Factor ◽

Transcription Factors ◽

Transcriptional Activation ◽

Current Knowledge ◽

Nuclear Architecture ◽

Subnuclear Localization ◽

Modular Structures

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

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Transcriptional Control of Parturition: Insights from Gene Regulation Studies in the Myometrium

MHR Basic science of reproductive medicine ◽

10.1093/molehr/gaab024 ◽

2021 ◽

Author(s):

Nawrah Khader ◽

Virlana M Shchuka ◽

Oksana Shynlova ◽

Jennifer A Mitchell

Keyword(s):

Transcription Factors ◽

Regulatory Networks ◽

Transcriptional Control ◽

Progesterone Receptors ◽

Activator Protein 1 ◽

Transcriptional Regulatory Networks ◽

Regulatory Pathways ◽

Transcriptional Regulatory ◽

Mechanistic Basis ◽

Labour Onset

Abstract The onset of labour is a culmination of a series of highly coordinated and preparatory physiological events that take place throughout the gestational period. In order to produce the associated contractions needed for fetal delivery, smooth muscle cells in the muscular layer of the uterus (i.e. myometrium) undergo a transition from quiescent to contractile phenotypes. Here, we present the current understanding of the roles transcription factors play in critical labour-associated gene expression changes as part of the molecular mechanistic basis for this transition. Consideration is given to both transcription factors that have been well-studied in a myometrial context, i.e. activator protein 1 (AP-1), progesterone receptors (PRs), estrogen receptors (ERs), and nuclear factor kappa B (NF-κB), as well as additional transcription factors whose gestational event-driving contributions have been demonstrated more recently. These transcription factors may form pregnancy- and labour- associated transcriptional regulatory networks in the myometrium to modulate the timing of labour onset. A more thorough understanding of the transcription factor-mediated, labour-promoting regulatory pathways holds promise for the development of new therapeutic treatments that can be used for the prevention of preterm labour in at-risk women.

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Interplay between cofactors and transcription factors in hematopoiesis and hematological malignancies

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00422-1 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zi Wang ◽

Pan Wang ◽

Yanan Li ◽

Hongling Peng ◽

Yu Zhu ◽

...

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Hematological Malignancies ◽

Current Knowledge ◽

Regulation Of Gene Expression ◽

Hematologic Disorders ◽

Cell Lineages ◽

Stage Of Development ◽

Transcription Complexes ◽

Insight Into

AbstractHematopoiesis requires finely tuned regulation of gene expression at each stage of development. The regulation of gene transcription involves not only individual transcription factors (TFs) but also transcription complexes (TCs) composed of transcription factor(s) and multisubunit cofactors. In their normal compositions, TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis. The integration of posttranslational and conformational modifications in the chromatin landscape, nucleosomes, histones and interacting components via the cofactor–TF interplay is critical to optimal TF activity. Mutations or translocations of cofactor genes are expected to alter cofactor–TF interactions, which may be causative for the pathogenesis of various hematologic disorders. Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy. In this review, we summarize the current knowledge regarding the models and functions of cofactor–TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies. This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.

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DNA-binding specificity of GATA family transcription factors.

Molecular and Cellular Biology ◽

10.1128/mcb.13.7.3999 ◽

1993 ◽

Vol 13 (7) ◽

pp. 3999-4010 ◽

Cited By ~ 448

Author(s):

M Merika ◽

S H Orkin

Keyword(s):

Transcription Factors ◽

Dna Binding ◽

Mammalian Cells ◽

Chimeric Protein ◽

Binding Specificity ◽

Mobility Shift ◽

Binding Domains ◽

Dna Binding Specificity ◽

Mobility Shift Assay ◽

Gata Family

GATA-binding proteins constitute a family of transcription factors that recognize a target site conforming to the consensus WGATAR (W = A or T and R = A or G). Here we have used the method of polymerase chain reaction-mediated random site selection to assess in an unbiased manner the DNA-binding specificity of GATA proteins. Contrary to our expectations, we show that GATA proteins bind a variety of motifs that deviate from the previously assigned consensus. Many of the nonconsensus sequences bind protein with high affinity, equivalent to that of conventional GATA motifs. By using the selected sequences as probes in the electrophoretic mobility shift assay, we demonstrate overlapping, but distinct, sequence preferences for GATA family members, specified by their respective DNA-binding domains. Furthermore, we provide additional evidence for interaction of amino and carboxy fingers of GATA-1 in defining its binding site. By performing cotransfection experiments, we also show that transactivation parallels DNA binding. A chimeric protein containing the finger domain of areA and the activation domains of GATA-1 is capable of activating transcription in mammalian cells through GATA motifs. Our findings suggest a mechanism by which GATA proteins might selectively regulate gene expression in cells in which they are coexpressed.

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Screening Driving Transcription Factors in the Processing of Gastric Cancer

Gastroenterology Research and Practice ◽

10.1155/2016/8431480 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Guangzhong Xu ◽

Kai Li ◽

Nengwei Zhang ◽

Bin Zhu ◽

Guosheng Feng

Keyword(s):

Gastric Cancer ◽

Transcription Factors ◽

Regulatory Network ◽

Target Genes ◽

Transcriptional Regulatory Network ◽

Expression Profiles ◽

Functional Enrichment ◽

Regulatory Mechanisms ◽

Integrated Analysis ◽

Transcriptional Regulatory

Background. Construction of the transcriptional regulatory network can provide additional clues on the regulatory mechanisms and therapeutic applications in gastric cancer.Methods. Gene expression profiles of gastric cancer were downloaded from GEO database for integrated analysis. All of DEGs were analyzed by GO enrichment and KEGG pathway enrichment. Transcription factors were further identified and then a global transcriptional regulatory network was constructed.Results. By integrated analysis of the six eligible datasets (340 cases and 43 controls), a bunch of 2327 DEGs were identified, including 2100 upregulated and 227 downregulated DEGs. Functional enrichment analysis of DEGs showed that digestion was a significantly enriched GO term for biological process. Moreover, there were two important enriched KEGG pathways: cell cycle and homologous recombination. Furthermore, a total of 70 differentially expressed TFs were identified and the transcriptional regulatory network was constructed, which consisted of 566 TF-target interactions. The top ten TFs regulating most downstream target genes were BRCA1, ARID3A, EHF, SOX10, ZNF263, FOXL1, FEV, GATA3, FOXC1, and FOXD1. Most of them were involved in the carcinogenesis of gastric cancer.Conclusion. The transcriptional regulatory network can help researchers to further clarify the underlying regulatory mechanisms of gastric cancer tumorigenesis.

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Dissecting the Repertoire of DNA-Binding Transcription Factors of the Archaeon Pyrococcus furiosus DSM 3638

Life ◽

10.3390/life8040040 ◽

2018 ◽

Vol 8 (4) ◽

pp. 40 ◽

Cited By ~ 2

Author(s):

Antonia Denis ◽

Mario Alberto Martínez-Núñez ◽

Silvia Tenorio-Salgado ◽

Ernesto Perez-Rueda

Keyword(s):

Transcription Factors ◽

Dna Binding ◽

Regulatory Networks ◽

Pyrococcus Furiosus ◽

Structural Domain ◽

Transcriptional Regulatory Networks ◽

Dna Binding Domains ◽

Binding Domains ◽

Transcriptional Regulatory ◽

Cellular Domain

In recent years, there has been a large increase in the amount of experimental evidence for diverse archaeal organisms, and these findings allow for a comprehensive analysis of archaeal genetic organization. However, studies about regulatory mechanisms in this cellular domain are still limited. In this context, we identified a repertoire of 86 DNA-binding transcription factors (TFs) in the archaeon Pyrococcus furiosus DSM 3638, that are clustered into 32 evolutionary families. In structural terms, 45% of these proteins are composed of one structural domain, 41% have two domains, and 14% have three structural domains. The most abundant DNA-binding domain corresponds to the winged helix-turn-helix domain; with few alternative DNA-binding domains. We also identified seven regulons, which represent 13.5% (279 genes) of the total genes in this archaeon. These analyses increase our knowledge about gene regulation in P. furiosus DSM 3638 and provide additional clues for comprehensive modeling of transcriptional regulatory networks in the Archaea cellular domain.

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