GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland.

Steger, David J.; Hecht, Jonathan H.; Mellon, Pamela L.

doi:10.1128/mcb.14.8.5592

Cited by 173 publications

(113 citation statements)

References 66 publications

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“…Chromogranin A promoter progressive 5' deletion mutant/luciferase reporter plasmids (pXPl 133, pXP426, pXP147, pXPlOO, pXP77, or pXP61), or a CRE box site-directed mutant plasmid ( protein hormone a subunit (32,34), and renin (33,36), although not all of these cAMP effects have been clearly shown to be transcriptional (26-28, 30, 33). Furthermore, CRE sites have been implicated in the cell type-specific expression of the DBH (34), glycoprotein hormone a subunit (35), and renin (36) genes. Mutation of CRE sites in those genes causes a significant decline in promoter activity in the appropriate cell type, similar to the results presented here for the chromogranin A promoter (Figs.…”

Section: Discussionmentioning

confidence: 99%

A functional cyclic AMP response element plays a crucial role in neuroendocrine cell type-specific expression of the secretory granule protein chromogranin A.

Wu¹,

Mahata²,

Mahata³

et al. 1995

J. Clin. Invest.

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Chromogranin A, a soluble acidic protein, is a ubiquitous component of secretory vesicles throughout the neuroendocrine system. We reported previously the cloning and initial characterization of the mouse chromogranin A gene promoter, which showed that the promoter contains both positive and negative domains and that a proximal promoter spanning nucleotides -147 to +42 bp relative to the transcriptional start site is sufficient for neuroendocrine cell type-specific expression. The current study was undertaken to identify the particular elements within this proximal promoter that control tissue-specific expression. We found that deletion or point mutations in the potential cAMP response element (CRE) site at -68 bp virtually abolished promoter activity specifically in neuroendocrine (PC12 chromaffin or AtT20 corticotrope) cells, with little effect on activity in control (NIH3T3 fibroblast) cells; thus, the CRE box is necessary for neuroendocrine cell type-specific activity of the chromogranin A promoter. Furthermore, the effect of the CRE site is enhanced in the context of intact (wild-type) promoter sequences between -147 and -100 bp. DNase I footprint analysis showed that these regions (including the CRE box) bind nuclear proteins present in both neuroendocrine (AtT20) and control (NIH3T3) cells. In AtT20 cells, electrophoretic mobility shift assays and factor-specific antibody supershifts showed that an oligonucleotide containing the chromogranin A CRE site formed a single, homogeneous protein-DNA complex containing the CRE-binding protein CREB. However, in control NIH3T3 cells we found evidence for an additional immunologically unrelated protein in this complex. A single copy of this oligonucleotide was able to confer neuroendocrine-specific expression to a heterologous (thymidine kinase) promoter, albeit with less fold selectivity than the full proximal chromogranin A promoter. Hence, the CRE site was partially sufficient to explain the neuroendocrine cell type specificity of the promoter. The functional activity of the CRE site was confirmed through studies of the endogenous chromogranin A gene. Northern mRNA analysis showed that expression of the endogenous chromogranin A gene was stimulated seven-to eightfold by cAMP in PC12 cells, whereas no induction occurred in the

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Section: Discussionmentioning

confidence: 99%

A functional cyclic AMP response element plays a crucial role in neuroendocrine cell type-specific expression of the secretory granule protein chromogranin A.

Wu¹,

Mahata²,

Mahata³

et al. 1995

J. Clin. Invest.

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“…GATA factors have been shown to functionally interact with other classes of transcription factors such as AP1 (25), Sp1 (26 -28), and the estrogen receptor (29). The AGATAA sequence is also present in the human, equine, and mouse ␣-subunit promoters, and Steger et al (30) have shown that GATA family members are involved in both pituitary and placental expression of the ␣-glycoprotein hormone gene that encodes the common subunit of TSH, follicle-stimulating hormone, luteinizing hormone, and chorionic gonadotropin. In the current study, we present data showing that the 50-kDa protein in thyrotropes that binds to the proximal P1 region of the mTSH␤ promoter and functionally synergizes with Pit-1 is likely to be GATA-2.…”

mentioning

confidence: 99%

Pit-1 and GATA-2 Interact and Functionally Cooperate to Activate the Thyrotropin β-Subunit Promoter

Gordon

Lewis

Haugen

et al. 1997

Journal of Biological Chemistry

128

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The molecular determinants governing cell-specific expression of the thyrotropin (TSH) ␤-subunit gene in pituitary thyrotropes are not well understood. The P1 region of the mouse TSH␤ promoter (؊133 to ؊88) region interacts with Pit-1 and an additional 50-kDa factor at an adjacent site that resembles a consensus GATA binding site. Northern and Western blot assays demonstrated the presence of GATA-2 transcripts and protein in TtT-97 thyrotropic tumors. In electrophoretic mobility shift assays, a comigrating complex was observed with both TtT-97 nuclear extracts and GATA-2 expressed in COS cells. The complex demonstrated binding specificity to the P1 region DNA probe and could be disrupted by a GATA-2 antibody. When both Pit-1 and GATA-2 were combined, a slower migrating complex, indicative of a ternary protein-DNA interaction was observed. Cotransfection of both Pit-1 and GATA-2 into CV-1 cells synergistically stimulated mouse TSH␤ promoter activity 8.5-fold, while each factor alone had a minimal effect. Mutations that abrogated this functional stimulatory effect mapped to the P1 region. Finally, we show that GATA-2 directly interacts with Pit-1 in solution. In summary, these data demonstrate functional synergy and physical interaction between homeobox and zinc finger factors and provide insights into the transcriptional mechanisms of thyrotrope-specific gene expression.Cell-specific expression of eukaryotic genes involves the functional interaction of sets of transcription factors that interact with essential cis-acting promoter regions to initiate RNA transcription. The repertoires of transcription factors that are involved in the expression of genes in highly differentiated cells often consist of those ubiquitously expressed in many cell types in cooperation with others whose expression are cell type-restricted (1, 2). Expression of the thyrotropin (TSH) 1

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“…Placenta-specific transcriptional controls fall into two broad categories: first, they may share the same promoter as other tissues, but utilize placenta-specific enhancers or upstream elements as observed for glycoprotein hormone ␣ subunit, CS-B, adenosine deaminase (ADA), and leptin genes (28,29,32,38,39); second, they may utilize both placenta-specific promoters and enhancers, as previously shown for the aromatase gene (33) and as we now show for the LIFR gene.…”

Section: Discussionmentioning

confidence: 94%

“…5A, lanes 5-8 and lanes [15][16][17][18]. Specific complexes between the known GATA oligo with JEG-3 nuclear extract were supershifted by antibody to GATA-2, -3, or -4, indicating the capability of the known GATA oligo to bind to GATA-2, -3, or -4 proteins, which are known to be present in JEG-3 cells (32,34). In contrast, specific complexes between the oligo b and JEG-3 nuclear extract could not be supershifted by antibody to GATA-2, -3, or -4, indicating that these specific complexes involved a protein other than GATA-2, -3, or -4 recognizing region B.…”

Section: Linker Analysis Revealsmentioning

confidence: 99%

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Functional Map of a Placenta-specific Enhancer of the Human Leukemia Inhibitory Factor Receptor Gene

Wang

Melmed

1998

Journal of Biological Chemistry

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We recently reported a placenta-specific enhancer in the human leukemia inhibitory factor receptor (LIFR) gene and now show detailed characterization of the 226-base pair enhancer (؊4625/؊4400 nucleotides). Four of twenty-two mutants in linker analysis showed reduced promoter activities to 45, 30, 10, and 10%, respectively. Specific binding of region A (؊4617/؊4602) with nuclear extract was competed by a known Oct-1 oligo and supershifted by Oct-1 antibody. Specific binding of region B (؊4549/؊4535) was competed by a GATA oligo, but could not be supershifted by four GATA antibodies. Nevertheless, mutagenesis showed that critical bases in region B were identical to the GATA core motif, indicating that region B may bind to a novel GATA family transcription factor. The other two adjacent regions designated as region C (؊4464/؊4445) showed no known consensus binding sites, and their specific placental JEG-3 nuclear extract binding was not evident in nonplacental nuclear extracts and was not competed by a trophoblast specific element (TSE), indicating that region C is a novel placenta-specific element (PSE, CATTTCCTGAACTAGTT-TTT). Footprinting localized the binding boundary of PSE-binding protein (PSEB), and three Gs were found to be important for specific PSE binding. UV cross-linking showed that PSEB had a molecular mass of ϳ160 kDa, substituting the PSE with two previously reported placenta elements TSE or chorionic somatomammotropin enhancer factor 1 (CSEF-1) motifs resulted in markedly different promoter activities, indicating that PSEB is indeed different from TSE binding protein or CSEF-1. These results are the first demonstration that a novel PSE is the major element for placenta-specific enhancer activity in human LIFR gene.

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GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland.

Cited by 173 publications

References 66 publications

A functional cyclic AMP response element plays a crucial role in neuroendocrine cell type-specific expression of the secretory granule protein chromogranin A.

A functional cyclic AMP response element plays a crucial role in neuroendocrine cell type-specific expression of the secretory granule protein chromogranin A.

Pit-1 and GATA-2 Interact and Functionally Cooperate to Activate the Thyrotropin β-Subunit Promoter

Functional Map of a Placenta-specific Enhancer of the Human Leukemia Inhibitory Factor Receptor Gene

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