The regulator of early gliogenesis
            <i>glial cells missing</i>
            is a transcription factor with a novel type of DNA-binding domain

Schreiber, Jörg; Sock, Elisabeth; Wegner, Michael

doi:10.1073/pnas.94.9.4739

Cited by 111 publications

(87 citation statements)

References 28 publications

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“…Two groups have determined binding sites for the Drosophila GCM protein by binding site selection assays (18,28). When aligned, the two proposed GCM binding sites and TSE2 look similar (Fig.…”

Section: Resultsmentioning

confidence: 99%

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A GCM Motif Protein Is Involved in Placenta-specific Expression of Human Aromatase Gene

Yamada

Ogawa²,

Honda

et al. 1999

Journal of Biological Chemistry

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A new cis-element, trophoblast-specific element 2 (TSE2) is located in the placenta-specific enhancer of the human aromatase gene that dictates its tissue-specific expression. In the minimum enhancer region, an element similar to the trophoblast-specific element (TSE), originally described for the human chorionic gonadotropin ␣-subunit gene, also exists (Yamada, K., Harada, N., Honda, S., and Takagi, Y. (1995) J. Biol. Chem. 270, 25064 -25069). The co-presence of TSE and TSE2 is required to direct trophoblast-specific expression driven by a heterologous thymidine kinase promoter. A 2562-base pair cDNA clone encoding a 436-amino acid protein that binds to TSE2 was isolated from a human placental cDNA library using a yeast one-hybrid system with the TSE2 as a reporter sequence. The protein was revealed to be identical to hGCMa, a mammalian homologue of the Drosophila GCM (glia cells missing) protein. Expression of hGCMa is restricted to the placenta. The protein also binds to PLE1 in the leptin promoter among other cis-elements reported to confer placenta-specific expression, suggesting that hGCMa is a placenta-specific transcription regulator, possibly involved in the expression of multiple placenta-specific genes.

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Section: Resultsmentioning

confidence: 99%

“…The DNA sequence that binds Drosophila GCM has been determined by binding site selection assay by two groups (18,28). The core sequence we determined independently for TSE2BP is similar.…”

Section: Discussionmentioning

confidence: 99%

A GCM Motif Protein Is Involved in Placenta-specific Expression of Human Aromatase Gene

Yamada

Ogawa²,

Honda

et al. 1999

Journal of Biological Chemistry

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“…It is still unclear whether Gcm1 regulates the Cebpa and Synb genes directly or indirectly. However, Gcm1 is a transcriptional activator (Akiyama et al, 1996;Chang et al, 2005;Schreiber et al, 1997;Schubert et al, 2004) and both Cebpa and Synb contain Gcm1 binding sites within their regulatory regions. Within 10 kb upstream of the Cebpa transcriptional start site, there are seven predicted Gcm1 binding sites at -9256, -7558, -6335, -5842, -5275, -5231 and -1861, whereas within the same region upstream of Synb, there are eight at -6496, -3178, -2656, -2634, -1864, -1767, -866 and -769.…”

Section: Research Articlementioning

confidence: 99%

Early patterning of the chorion leads to the trilaminar trophoblast cell structure in the placental labyrinth

et al. 2008

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The labyrinth of the rodent placenta contains villi that are the site of nutrient exchange between mother and fetus. They are covered by three trophoblast cell types that separate the maternal blood sinusoids from fetal capillaries -a single mononuclear cell that is a subtype of trophoblast giant cell (sinusoidal or S-TGC) with endocrine function and two multinucleated syncytiotrophoblast layers, each resulting from cell-cell fusion, that function in nutrient transport. The developmental origins of these cell types have not previously been elucidated. We report here the discovery of cell-layer-restricted genes in the mid-gestation labyrinth (E12.5-14.5) including Ctsq in S-TGCs (also Hand1-positive), Syna in syncytiotrophoblast layer I (SynT-I), and Gcm1, Cebpa and Synb in syncytiotrophoblast layer II (SynT-II). These genes were also expressed in distinct layers in the chorion as early as E8.5, prior to villous formation. Specifically, Hand1 was expressed in apical cells lining maternal blood spaces (Ctsq is not expressed until E12.5), Syna in a layer immediately below, and Gcm1, Cebpa and Synb in basal cells in contact with the allantois. Cebpa and Synb were co-expressed with Gcm1 and were reduced in Gcm1 mutants. By contrast, Hand1 and Syna expression was unaltered in Gcm1 mutants, suggesting that Gcm1-positive cells are not required for the induction of the other chorion layers. These data indicate that the three differentiated trophoblast cell types in the labyrinth arise from distinct and autonomous precursors in the chorion that are patterned before morphogenesis begins.

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“…Altogether these GCM homologues form a novel family of transcription factors, which all share sequence homology in the amino-terminal region that constitutes the DNA-binding domain called the GCM motif. Although sequence homology is less preserved outside the GCM motif, a transactivation domain (TAD) has been identified in the extreme carboxyl terminus of GCM proteins (10,11). The optimal recognition sequence for the GCM motif is 5Ј-(A/ G)CCC(T/G)CAT-3Ј or its 5Ј-ATG(A/C)GGG(T/C)-3Ј complement (10,12).…”

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confidence: 99%

GCMa Regulates the Syncytin-mediated Trophoblastic Fusion

Yu¹,

Shen²,

Lin³

et al. 2002

Journal of Biological Chemistry

247

208

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The human placental trophoblast cell can be classified as either a cytotrophoblast or a syncytiotrophoblast. Cytotrophoblasts can function as stem cells for the development of the syncytiotrophoblast layer via cell fusion. An envelope gene of the human endogenous retrovirus family W (HERV-W) called syncytin is specifically expressed in the syncytiotrophoblast layer. Syncytin is a fusogenic membrane protein; therefore, it can mediate the fusion of cytotrophoblasts into the syncytiotrophoblast layer, which is essential for pregnancy maintenance. GCMa is a placenta-specific transcription factor and is required for placental development. To study the placenta-specific fusion mediated by syncytin, we tested whether GCMa is involved in this process by regulating syncytin gene expression. In this report, we demonstrate that GCMa was able to regulate syncytin gene expression via two GCMa-binding sites upstream of the 5-long terminal repeat of the syncytin-harboring HERV-W family member in BeWo and JEG3 cells but not in HeLa cells. Furthermore, adenovirus-directed expression of GCMa enhanced syncytin gene expression and syncytinmediated cell fusion in BeWo and JEG3 cells but not in HeLa cells. Therefore, the integration site of the syncytin-harboring HERV-W family member in the human genome is close to the functional GCMa-binding sites by which GCMa can specifically transactivate syncytin gene expression in trophoblast cells. Our results may help to explain the mechanism underlying the cell fusion event specific for syncytiotrophoblast formation.The human placenta contains a specialized cell type called a trophoblast, which is the first lineage to differentiate in embryo development and plays key roles during implantation and placentation. The human trophoblast cell can be further classified as cytotrophoblasts and syncytiotrophoblasts. In the early gestation stage, cytotrophoblast stem cells facing the maternal decidua proliferate and fuse to form a syncytium, i.e. the syncytiotrophoblast. Later on, vascular spaces called trophoblastic lacunae appear in the syncytium around day 8 -9. The cytotrophoblast layer under the syncytium can rapidly proliferate into these spaces, which results in the formation of the primary chorionic villi. Subsequently, proliferation of the cytotrophoblasts, growth of chorionic mesoderm (under the cytotrophoblast layer), and blood vessel development transform the primary villi into secondary and tertiary villi, which are composed of a core of mesenchyme cells surrounded by an inner layer of cytotrophoblasts and an outer layer of multinucleate syncytiotrophoblasts (1, 2). The syncytiotrophoblast layer (syncytium) transports nutrients and gases and produces hormones such as placental lactogen and chorionic gonadotrophin, which are indispensable for the further progression of pregnancy (1).Recently, a membrane protein termed syncytin has been demonstrated to mediate cell fusion of the human BeWo trophoblastic cell line (3). Syncytin is an envelope protein of the newly identified human endogenous ...

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The regulator of early gliogenesis glial cells missing is a transcription factor with a novel type of DNA-binding domain

Cited by 111 publications

References 28 publications

A GCM Motif Protein Is Involved in Placenta-specific Expression of Human Aromatase Gene

A GCM Motif Protein Is Involved in Placenta-specific Expression of Human Aromatase Gene

Early patterning of the chorion leads to the trilaminar trophoblast cell structure in the placental labyrinth

GCMa Regulates the Syncytin-mediated Trophoblastic Fusion

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