Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The GATA-1 transcription factor has been shown to be important in the regulation of globin and non-globin genes in erythroid, megakaryocytic and mast cell lineages. It is a member of a family of GATA proteins which both overlap in their expression patterns and bind the motif (A/T)GATA(A/G). The GATA family of proteins are also members of the superfamily of zinc finger-like domain proteins and have two similar domains of the type Cys-X2-Cys-X17-Cys-X2-Cys which direct the DNA binding of the protein. A random oligonucleotide selection procedure has been employed to further elucidate the mechanism of GATA-1-DNA recognition. The resulting oligonucleotides were tested for binding activity to both wild-type and mutant GATA-1 proteins. Two classes of GATA-1-DNA interaction have been defined, the first requiring only the carboxy finger of GATA-1 to bind and having the motif GAT(A/T), the second requiring both finger domains to bind and having the core motif (T/C)AAG. By using sequence comparison and depurination analysis it is concluded that the two finger-like domains of GATA-1 have different DNA binding recognition motifs. Binding of GATA-1 to GAT(A/T) motifs is associated with transcriptional activation of linked genes. The only known (T/C)AAG motif is in the distal CAAT-box promoter region of the human A gamma-globin gene where the binding of GATA-1 appears to regulate the correct developmental suppression of gamma-globin expression.
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PMID:The two zinc finger-like domains of GATA-1 have different DNA binding specificities. 826 42

We report that embryonic stem cells efficiently undergo differentiation in vitro to mesoderm and hematopoietic cells and that this in vitro system recapitulates days 6.5 to 7.5 of mouse hematopoietic development. Embryonic stem cells differentiated as embryoid bodies (EBs) develop erythroid precursors by day 4 of differentiation, and by day 6, more than 85% of EBs contain such cells. A comparative reverse transcriptase-mediated polymerase chain reaction profile of marker genes for primitive endoderm (collagen alpha IV) and mesoderm (Brachyury) indicates that both cell types are present in the developing EBs as well in normal embryos prior to the onset of hematopoiesis. GATA-1, GATA-3, and vav are expressed in both the EBs and embryos just prior to and/or during the early onset of hematopoiesis, indicating that they could play a role in the early stages of hematopoietic development both in vivo and in vitro. The initial stages of hematopoietic development within the EBs occur in the absence of added growth factors and are not significantly influenced by the addition of a broad spectrum of factors, including interleukin-3 (IL-3), IL-1, IL-6, IL-11, erythropoietin, and Kit ligand. At days 10 and 14 of differentiation, EB hematopoiesis is significantly enhanced by the addition of both Kit ligand and IL-11 to the cultures. Kinetic analysis indicates that hematopoietic precursors develop within the EBs in an ordered pattern. Precursors of the primitive erythroid lineage appear first, approximately 24 h before precursors of the macrophage and definitive erythroid lineages. Bipotential neutrophil/macrophage and multilineage precursors appear next, and precursors of the mast cell lineage develop last. The kinetics of precursor development, as well as the growth factor responsiveness of these early cells, is similar to that found in the yolk sac and early fetal liver, indicating that the onset of hematopoiesis within the EBs parallels that found in the embryo.
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PMID:Hematopoietic commitment during embryonic stem cell differentiation in culture. 841 45

The delayed early serum response gene T1 encodes glycoproteins of the immunoglobulin superfamily with significant sequence similarity to the type 1 interleukin-1 receptor. The T1 gene is transcribed in fibroblasts into an abundant 2.7-kilobase (kb) and a rare 5-kb mRNA in response to proliferation-inducing stimuli. It gives predominantly rise to the longer transcript in the bone marrow of adult mice and in cultured mast cells. Alternative 3' processing is responsible for the two mRNA forms. The short transcript encodes a secreted protein with marked similarity to the extracellular domain of the interleukin-1 receptor, whereas the long mRNA is translated into a protein with an additional putative transmembrane and an intracellular domain. Here we demonstrate that T1 transcription in mast cells and fibroblasts initiates at two different start sites which are 10.5 kb apart. The alternative first exons are both spliced to exon 2 which contains the translation start site. Northern blot analysis and primer extension experiments revealed that promoter usage is strictly cell type-specific. T1 transcription in mast cells is initiated exclusively at the distal promoter, whereas in fibroblasts both the short and the long T1 mRNA start at the proximal promoter. Two GATA-1 elements were identified in the 5'-flanking region of the mast cell-specific distal exon 1.
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PMID:Transcription of the interleukin-1 receptor-related T1 gene is initiated at different promoters in mast cells and fibroblasts. 855 May 46

Although GATA-binding transcription factors (GATA-1 and GATA-2) are strongly expressed in cultured mast cells (CMCs), their expression in mast cells within tissues has not been reported. We examined the expression of GATA-1 and GATA-2 in skin tissues of mice using Northern blot analysis and in situ hybridization. mRNA for GATA-2 but not for GATA-1 was expressed in skin mast cells of WB-+/+ embryos between days 15 and 17 postcoitum (pc). The expression was downregulated on and after day 18 pc. Skin mast cells did not express GATA-2 after birth either. When the number of skin mast cells was compared with the number of GATA-2 mRNA-expressing cells, GATA-2 mRNA appeared to be expressed by mast cells only when the number was increasing. When the mRNA expression of high-affinity IgE receptor beta-subunit and mast cell carboxypeptidase A was used as differentiation markers, the expression of these mRNAs continued even after the downregulation of GATA-2 expression. To clarify the relationship of the proliferation and GATA-2 expression, proliferating CMCs derived from WBB6F1-+/+ mice were transplanted into the peritoneal cavity of mast cell-deficient WBB6F1-W/Wv mice. The CMCs stopped both the proliferation and GATA-2 expression after the transplantation, suggesting the association of these two parameters in mast cells within tissues of mice.
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PMID:Abundant expression of transcription factor GATA-2 in proliferating but not in differentiated mast cells in tissues of mice: demonstration by in situ hybridization. 856 71

Phenotype of P815 mouse mast cells changes markedly during culture in the peritoneal cavity of syngenic BDF1 mice. The cells, cultured for 1 week in the peritoneal cavity of syngenic BDF1 mice, proliferate and express high levels of L-histidine decarboxylase (HDC) and mouse mast cell protease (MMCP)-6 mRNAs, indicating the ability of P815 cells to differentiate toward mature connective tissue mast cells. Peritoneal fluid aspirated from P815-inoculated BDF1 mouse and added to cultured P815 cells in vitro was also found to induce HDC mRNA expression, suggesting that at least some of the humoral factors in the peritoneal fluid induce HDC mRNA transcription. Among the erythroid transcription factors, P815 cells expressed GATA-2 but not GATA-1 mRNA before and after the intraperitoneal incubation. In contrast, the expression of NF-E2 subunit p45 disappeared, while expression of subunit mafK was markedly reduced after incubation. Cotransfection assays using HDC-luciferase reporter and p45 and/or mafK expression constructs showed that NF-E2 affects the transactivation of HDC gene. These results suggest that NF-E2 is also an important transcription factor in mast cell differentiation.
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PMID:Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoneal cavity incubation. 891 Apr 69

The murine delayed-early serum-responsive gene T1 encodes glycoproteins of the interleukin-1 receptor family. Transcriptional initiation in fibroblasts is regulated by c-Fos and gives rise to a rare 5-kb mRNA and an abundant 2.7-kb mRNA. These transcripts are translated into a receptor-like membrane-anchored protein and a secreted protein consisting only of the ectodomain. In mast cells, T1 gene transcription is initiated 10.5 kb further upstream than in fibroblasts and gives rise predominantly to the 5-kb transcript under normal growth conditions. Here we demonstrate that calcium ionophore stimulation of mast cells resulted in an upregulation of T1 gene expression and a switch from the long to the short T1 transcript. This was paralleled by the disappearance of the receptor-type T1 protein on the mast cell surface and the secretion of large amounts of the truncated T1 protein. c-Fos and a T1 enhancer, which have previously been identified to be essential for T1 expression in fibroblasts, were not required for calcium ionophore-mediated T1 gene upregulation. Overexpression of the transcription factor GATA-1 in mast cells caused elevated T1 synthesis. Three GATA elements were identified in the minimal GATA-responsive mast cell promoter. Mutational analysis revealed that all three GATA elements are involved in T1 gene expression. Point mutations within the middle GATA element eliminated promoter activity completely, while mutations of the distal and proximal GATA binding sites reduced promoter strength by factors of 2 and 5, respectively. Exogenous expression of GATA-1 was not sufficient to activate the mast cell-specific promoter in NIH 3T3 fibroblasts.
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PMID:GATA-Dependent expression of the interleukin-1 receptor-related T1 gene in mast cells. 971 Jun 16

The SCL gene, also known as tal-1, encodes a basic helix-loop-helix transcription factor that is pivotal for the normal development of all hematopoietic lineages. SCL is expressed in committed erythroid, mast, and megakaryocytic cells as well as in hematopoietic stem cells. Nothing is known about the regulation of SCL transcription in mast cells, and in other lineages GATA-1 is the only tissue-specific transcription factor recognized to regulate the SCL gene. We have therefore analyzed the molecular mechanisms underlying SCL expression in mast cells. In this paper, we demonstrate that SCL promoter 1a was regulated by GATA-1 together with Sp1 and Sp3 in a manner similar to the situation in erythroid cells. However, SCL promoter 1b was strongly active in mast cells, in marked contrast to the situation in erythroid cells. Full activity of promoter 1b was dependent on ETS and Sp1/3 motifs. Transcription factors PU.1, Elf-1, Sp1, and Sp3 were all present in mast cell extracts, bound to promoter 1b and transactivated promoter 1b reporter constructs. These data provide the first evidence that the SCL gene is a direct target for PU.1, Elf-1, and Sp3.
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PMID:Transcriptional regulation of the stem cell leukemia gene by PU.1 and Elf-1. 978 9

Key regulatory regions necessary for the expression of the gene encoding FcepsilonRI alpha-chain, a component of the high-affinity IgE receptor primarily responsible for IgE-dependent allergic response, were investigated. Two regions, -74/-69 and -55/-47, which contained binding motifs for proteins belonging to the Ets family and the GATA family, respectively, were shown to be necessary for the activation of the alpha-chain promoter. Both the regulatory elements enhanced the promoter activity only in alpha-chain-producing cells PT18 and RBL-2H3 (mast cell lines), indicating that the elements required specific trans-acting proteins present in the alpha-chain-producing cells. EMSA using nuclear extracts and in vitro-translated proteins revealed that Elf-1 and GATA-1 bound to the enhancer elements. This is the first report describing the regulation in the expression of the FcepsilonRI alpha-chain.
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PMID:The transcription factors Elf-1 and GATA-1 bind to cell-specific enhancer elements of human high-affinity IgE receptor alpha-chain gene. 1039 50

In this study, we have mapped the onset of hematopoietic development in the mouse embryo using colony-forming progenitor assays and PCR-based gene expression analysis. With this approach, we demonstrate that commitment of embryonic cells to hematopoietic fates begins in proximal regions of the egg cylinder at the mid-primitive streak stage (E7.0) with the simultaneous appearance of primitive erythroid and macrophage progenitors. Development of these progenitors was associated with the expression of SCL/tal-1 and GATA-1, genes known to be involved in the development and maturation of the hematopoietic system. Kinetic analysis revealed the transient nature of the primitive erythroid lineage, as progenitors increased in number in the developing yolk sac until early somite-pair stages of development (E8.25) and then declined sharply to undetectable levels by 20 somite pairs (E9.0). Primitive erythroid progenitors were not detected in any other tissue at any stage of embryonic development. The early wave of primitive erythropoiesis was followed by the appearance of definitive erythroid progenitors (BFU-E) that were first detectable at 1-7 somite pairs (E8.25) exclusively within the yolk sac. The appearance of BFU-E was followed by the development of later stage definitive erythroid (CFU-E), mast cell and bipotential granulocyte/macrophage progenitors in the yolk sac. C-myb, a gene essential for definitive hematopoiesis, was expressed at low levels in the yolk sac just prior to and during the early development of these definitive erythroid progenitors. All hematopoietic activity was localized to the yolk sac until circulation was established (E8.5) at which time progenitors from all lineages were detected in the bloodstream and subsequently in the fetal liver following its development. This pattern of development suggests that definitive hematopoietic progenitors arise in the yolk sac, migrate through the bloodstream and seed the fetal liver to rapidly initiate the first phase of intraembryonic hematopoiesis. Together, these findings demonstrate that commitment to hematopoietic fates begins in early gastrulation, that the yolk sac is the only site of primitive erythropoiesis and that the yolk sac serves as the first source of definitive hematopoietic progenitors during embryonic development.
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PMID:Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. 1052 24

The cell type-specific expression of a gene is dependent on developmentally regulated modifications in chromatin structure that allow accessibility of basal and inducible transcription factors. In this study, we demonstrate that a cis-acting element in the second intron of the murine IL-4 gene has a dual function in regulating transcription in mast cells as well as chromatin accessibility of the IL-4 gene locus through its influence on the methylation state of the gene. Previous studies have shown that mast cell-restricted transcription factors GATA-1/2 and PU.1 associate with the intron element and regulate its activity. In this study, we use DNase I footprinting and mutational analyses to identify two additional sites that contribute to the element's ability to enhance transcription. One of these sites associates preferentially with STAT5a and STAT5b. We also demonstrate that deletion of the element or mutation of the GATA binding site in the context of a stably integrated IL-4 genomic construct prevents maintenance of a demethylated locus in IL-4-producing mast cells. These data indicate that, analogous to Ig and TCR intron regulatory elements, the intron enhancer has an essential role in maintaining developmentally regulated demethylation at the IL-4 gene locus. In addition, they indicate that members of the GATA family of transcription factors likely play an important role in these processes.
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PMID:An intron transcriptional enhancer element regulates IL-4 gene locus accessibility in mast cells. 1097 40


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