Mesoderm induction in Xenopus is a zygotic event regulated by maternal VegT via TGFbeta growth factors

Development ◽  
1999 ◽  
Vol 126 (24) ◽  
pp. 5759-5770 ◽  
Author(s):  
M. Kofron ◽  
T. Demel ◽  
J. Xanthos ◽  
J. Lohr ◽  
B. Sun ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factors ◽  
Body Axis ◽  
Mesoderm Induction ◽  
Equatorial Zone ◽  
Wild Type ◽  
Germ Layers ◽  
Endogenous Factors ◽  
Mesoderm Formation ◽  
Mesodermal Tissue

The maternal transcription factor VegT is important for establishing the primary germ layers in Xenopus. In previous work, we showed that the vegetal masses of embryos lacking maternal VegT do not produce mesoderm-inducing signals and that mesoderm formation in these embryos occurred ectopically, from the vegetal area rather than the equatorial zone of the blastula. Here we have increased the efficiency of the depletion of maternal VegT mRNA and have studied the effects on mesoderm formation. We find that maternal VegT is required for the formation of 90% of mesodermal tissue, as measured by the expression of mesodermal markers MyoD, cardiac actin, Xbra, Xwnt8 and alphaT4 globin. Furthermore, the transcription of FGFs and TGFbetas, Xnr1, Xnr2, Xnr4 and derriere does not occur in VegT-depleted embryos. We test whether these growth factors may be endogenous factors in mesoderm induction, by studying their ability to rescue the phenotype of VegT-depleted embryos, when their expression is restricted to the vegetal mass. We find that Xnr1, Xnr2, Xnr4 and derriere mRNA all rescue mesoderm formation, as well as the formation of blastopores and the wild-type body axis. Derriere rescues trunk and tail while nr1, nr2 and nr4 rescue head, trunk and tail. We conclude that mesoderm induction in Xenopus depends on a maternal transcription factor regulating these zygotic growth factors.

scholarly journals Identification in Xenopus of a structural homologue of the Drosophila gene snail

Development ◽  
1990 ◽  
Vol 109 (4) ◽  
pp. 967-973 ◽  
Author(s):  
M.G. Sargent ◽  
M.F. Bennett
Keyword(s):  
Transcription Factor ◽  
Zinc Fingers ◽  
Equatorial Zone ◽  
Zygotic Transcription ◽  
Mesoderm Formation ◽  
Calcium And Magnesium ◽  
Inducing Factors ◽  
Mesoderm Inducing Factors ◽  
Structural Homologue ◽  
Binding Loop

We have cloned a Xenopus cDNA that is related to snail, a gene that is required for mesoderm formation in Drosophila. The cDNA encodes a protein that contains five zinc-fingers that closely resemble those of snail. In the non-canonical parts of the DNA-binding loop, there is almost 90% homology between snail and xsna. The corresponding mRNA (xsna) is expressed strongly at the start of zygotic transcription simultaneously with the transcription factor EF1 alpha. In early gastrulae, xsna is equally distributed between the dorsal and ventral halves of the equatorial zone. The possibility that the capacity to synthesise xsna is more localised before the start of zygotic transcription has been investigated by culturing fragments of stage 8 embryos until xsna is synthesised. The capacity to synthesise xsna at stage 8 is located principally in the dorsal half of the equatorial zone. A small amount of maternal xsna is localised in the vegetal hemisphere before zygotic transcription starts. xsna is not present in isolated animal caps but can be induced by the mesoderm-inducing factors XTC-MIF and bFGF. Synthesis of xsna does not occur autonomously in dispersed cells but is restored when cells reaggregate in the presence of calcium and magnesium.

Transcription factor CHF1/Hey2 regulates the global transcriptional response to platelet-derived growth factor in vascular smooth muscle cells

2007 ◽  
Vol 30 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Shervin M. Shirvani ◽  
Linette Mookanamparambil ◽  
Marco F. Ramoni ◽  
Michael T. Chin
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Smooth Muscle ◽  
Growth Factors ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Platelet Derived Growth Factor ◽  
Expression Data ◽  
Wild Type ◽  
Muscle Response

The cardiovascular restricted transcription factor CHF1/Hey2 has been previously shown to regulate the smooth muscle response to growth factors. To determine how CHF1/Hey2 affects the smooth muscle response to growth factors, we performed a genomic screen for transcripts that are differentially expressed in wild-type and knockout smooth muscle cells after stimulation with platelet-derived growth factor. We screened 45,101 probes representing >39,000 transcripts derived from at least 34,000 genes, at eight different time points. We analyzed the expression data utilizing an algorithm based on Bayesian statistics to derive the best polynomial clustering model to fit the expression data. We found that in a total of 9,827 transcripts the normalized ratio of knockout to wild-type expression diverged more than threefold from baseline in at least one time point, and these transcripts separated into 17 distinct clusters. Further analysis of each cluster revealed distinct alterations in gene expression patterns for immediate early genes, transcription factors, matrix metalloproteinases, signaling molecules, and other molecules important in vascular biology. Our findings demonstrate that CHF1/Hey2 profoundly affects vascular smooth muscle phenotype by altering both the absolute expression level of a variety of genes and the kinetics of growth factor-induced gene expression.

scholarly journals The Transcription Factor RFX3 Directs Nodal Cilium Development and Left-Right Asymmetry Specification

2004 ◽  
Vol 24 (10) ◽  
pp. 4417-4427 ◽  
Author(s):  
E. Bonnafe ◽  
M. Touka ◽  
A. AitLounis ◽  
D. Baas ◽  
E. Barras ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Immune System ◽  
Intraflagellar Transport ◽  
Body Axis ◽  
High Rate ◽  
Ciliated Cells ◽  
Wild Type ◽  
Left Right Asymmetry ◽  
First Time ◽  
Deficient Mice

ABSTRACT There are five members of the RFX family of transcription factors in mammals. While RFX5 plays a well-defined role in the immune system, the functions of RFX1 to RFX4 remain largely unknown. We have generated mice with a deletion of the Rfx3 gene. RFX3-deficient mice exhibit frequent left-right (LR) asymmetry defects leading to a high rate of embryonic lethality and situs inversus in surviving adults. In vertebrates, specification of the LR body axis is controlled by monocilia in the embryonic node, and defects in nodal cilia consequently result in abnormal LR patterning. Consistent with this, Rfx3 is expressed in ciliated cells of the node and RFX3-deficient mice exhibit a pronounced defect in nodal cilia. In contrast to the case for wild-type embryos, for which we document for the first time a twofold increase in the length of nodal cilia during development, the cilia are present but remain markedly stunted in mutant embryos. Finally, we show that RFX3 regulates the expression of D2lic, the mouse orthologue of a Caenorhabditis elegans gene that is implicated in intraflagellar transport, a process required for the assembly and maintenance of cilia. In conclusion, RFX3 is essential for the differentiation of nodal monocilia and hence for LR body axis determination.

Chemotaxis and Transcription Factor Activation of Wild-Type and CCR6-Transfected RLE-6TN

Pneumologie ◽  
2012 ◽  
Vol 66 (11) ◽  
Author(s):  
K Hoehne ◽  
H Eibel ◽  
M Grimm ◽  
M Idzko ◽  
J Müller-Quernheim ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Wild Type ◽  
Transcription Factor Activation

scholarly journals Transcriptional Activation in Yeast Cells Lacking Transcription Factor IIA

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1573-1581 ◽  
Author(s):  
Susanna Chou ◽  
Sukalyan Chatterjee ◽  
Mark Lee ◽  
Kevin Struhl
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Large Subunit ◽  
Yeast Cells ◽  
Specific Cell ◽  
Wild Type ◽  
Activation Domains ◽  
Cycle Arrest ◽  
General Transcription Factor

Abstract The general transcription factor IIA (TFIIA) forms a complex with TFIID at the TATA promoter element, and it inhibits the function of several negative regulators of the TATA-binding protein (TBP) subunit of TFIID. Biochemical experiments suggest that TFIIA is important in the response to transcriptional activators because activation domains can interact with TFIIA, increase recruitment of TFIID and TFIIA to the promoter, and promote isomerization of the TFIID-TFIIA-TATA complex. Here, we describe a double-shut-off approach to deplete yeast cells of Toa1, the large subunit of TFIIA, to <1% of the wild-type level. Interestingly, such TFIIA-depleted cells are essentially unaffected for activation by heat shock factor, Ace1, and Gal4-VP16. However, depletion of TFIIA causes a general two- to threefold decrease of transcription from most yeast promoters and a specific cell-cycle arrest at the G2-M boundary. These results indicate that transcriptional activation in vivo can occur in the absence of TFIIA.

scholarly journals RUNX1 and REXO2 are associated with the heterogeneity and prognosis of IDH wild type lower grade glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Transcription Factor ◽  
Low Frequency ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Wild Type ◽  
Lower Grade Glioma ◽  
Cancer Genome Atlas ◽  
Worse Prognosis ◽  
Genome Atlas

AbstractBased on isocitrate dehydrogenase (IDH) alterations, lower grade glioma (LGG) is divided into IDH mutant and wild type subgroups. However, the further classification of IDH wild type LGG was unclear. Here, IDH wild type LGG patients in The Cancer Genome Atlas and Chinese Glioma Genome Atlas were divided into two sub-clusters using non-negative matrix factorization. IDH wild type LGG patients in sub-cluster2 had prolonged overall survival and low frequency of CDKN2A alterations and low immune infiltrations. Differentially expressed genes in sub-cluster1 were positively correlated with RUNX1 transcription factor. Moreover, IDH wild type LGG patients with higher stromal score or immune score were positively correlated with RUNX1 transcription factor. RUNX1 and its target gene REXO2 were up-regulated in sub-cluster1 and associated with the worse prognosis of IDH wild type LGG. RUNX1 and REXO2 were associated with the higher immune infiltrations. Furthermore, RUNX1 and REXO2 were correlated with the worse prognosis of LGG or glioma. IDH wild type LGG in sub-cluster2 was hyper-methylated. REXO2 hyper-methylation was associated with the favorable prognosis of LGG or glioma. At last, we showed that, age, tumor grade and REXO2 expression were independent prognostic factors in IDH wild type LGG.

scholarly journals The AML-associated K313 mutation enhances C/EBPα activity by leading to C/EBPα overexpression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ian Edward Gentle ◽  
Isabel Moelter ◽  
Mohamed Tarek Badr ◽  
Konstanze Döhner ◽  
Michael Lübbert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Culture ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activity ◽  
Target Gene ◽  
Wild Type ◽  
Elevated Expression ◽  
Factor C ◽  
Acute Myeloid

AbstractMutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.

Role of heat shock transcription factor in yeast metallothionein gene expression

1991 ◽  
Vol 11 (7) ◽  
pp. 3676-3681
Author(s):  
W M Yang ◽  
W Gahl ◽  
D Hamer
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Heat Shock ◽  
Gene Transcription ◽  
Heat Shock Factor ◽  
Heat Shock Transcription Factor ◽  
Wild Type ◽  
Promoter Sequences ◽  
Metallothionein Gene ◽  
Upstream Promoter

The induction of Saccharomyces cerevisiae metallothionein gene transcription by Cu and Ag is mediated by the ACE1 transcription factor. In an effort to detect additional stimuli and factors that regulate metallothionein gene transcription, we isolated a Cu-resistant suppressor mutant of an ACE1 deletion strain. Even in the absence of metals, the suppressor mutant exhibited high basal levels of metallothionein gene transcription that required upstream promoter sequences. The suppressor gene was cloned, and its predicted product was shown to correspond to yeast heat shock transcription factor with a single-amino-acid substitution in the DNA-binding domain. The mutant heat shock factor bound strongly to metallothionein gene upstream promoter sequences, whereas wild-type heat shock factor interacted weakly with the same region. Heat treatment led to a slight but reproducible induction of metallothionein gene expression in both wild-type and suppressor strains, and Cd induced transcription in the mutant strain. These studies provide evidence for multiple pathways of metallothionein gene transcriptional regulation in S. cerevisiae.

Expression of a novel FGF in the Xenopus embryo. A new candidate inducing factor for mesoderm formation and anteroposterior specification

Development ◽  
1992 ◽  
Vol 114 (3) ◽  
pp. 711-720 ◽  
Author(s):  
H.V. Isaacs ◽  
D. Tannahill ◽  
J.M. Slack
Keyword(s):  
Specific Activity ◽  
Biological Properties ◽  
The Body ◽  
Mesoderm Induction ◽  
Gastrula Stage ◽  
Blastula Stage ◽  
Mesoderm Formation ◽  
Low Levels

We have cloned and sequenced a new member of the fibroblast growth factor family from Xenopus laevis embryo cDNA. It is most closely related to both mammalian kFGF (FGF-4) and FGF-6 but as it is not clear whether it is a true homologue of either of these genes we provisionally refer to it as XeFGF (Xenopus embryonic FGF). Two sequences were obtained, differing by 11% in derived amino acid sequence, which probably represent pseudotetraploid variants. Both the sequence and the behaviour of in vitro translated protein indicates that, unlike bFGF (FGF-2), XeFGF is a secreted molecule. Recombinant XeFGF protein has mesoderm-inducing activity with a specific activity similar to bFGF. XeFGF mRNA is expressed maternally and zygotically with a peak during the gastrula stage. Both probe protection and in situ hybridization showed that the zygotic expression is concentrated in the posterior of the body axis and later in the tailbud. Later domains of expression were found near the midbrain/hindbrain boundary and at low levels in the myotomes. Because of its biological properties and expression pattern, XeFGF is a good candidate for an inducing factor with possible roles both in mesoderm induction at the blastula stage and in the formation of the anteroposterior axis at the gastrula stage.

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