A GATA Box in the <i>GATA-1</i> Gene Hematopoietic Enhancer Is a Critical Element in the Network of GATA Factors and Sites That Regulate This Gene

Nishimura, Shigeko; Takahashi, Satoru; Kuroha, Takashi; Suwabe, Naruyoshi; Nagasawa, Toshiro; Trainor, Cecelia D.; Yamamoto, Masayuki

doi:10.1128/mcb.20.2.713-723.2000

Cited by 113 publications

(153 citation statements)

References 36 publications

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“…This suggested that the -16.5 ECR element can potentially play an important role in in vivo CCL2 transcriptional regulation. We found the enhancer activity exhibited by the -16.5 ECR to be orientation-dependent, which deviates from the operational definition of an enhancer (42)(43)(44). However, enhancers that are orientation-dependent for their function have previously been reported (45,46).…”

Section: Discussioncontrasting

confidence: 47%

An Evolutionarily Conserved TNF-α–Responsive Enhancer in the Far Upstream Region of Human CCL2 Locus Influences Its Gene Expression

Bonello

Pham

Begum

et al. 2011

The Journal of Immunology

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Comparative cross-species genomic analysis has served as a powerful tool to discover novel noncoding regulatory regions that influence gene expression in several cytokine loci. In this study, we have identified several evolutionarily conserved regions (ECRs) that are shared between human, rhesus monkey, dog, and horse and that are upstream of the promoter regions that have been previously shown to play a role in regulating CCL2 gene expression. Of these, an ECR that was ∼16.5 kb (−16.5 ECR) upstream of its coding sequence contained a highly conserved NF-κB site. The region encompassing the −16.5 ECR conferred TNF-α responsiveness to homologous and heterologous promoters. In vivo footprinting demonstrated that specific nucleotide residues in the –16.5 ECR were protected or became hypersensitive after TNF-α treatment. The footprinted regions were found to bind NF-κB subunits in vitro and in vivo. Mutation/deletion of the conserved NF-κB binding site in the −16.5 ECR led to loss of TNF-α responsiveness. After TNF-α stimulation, the –16.5 ECR showed increased sensitivity to nuclease digestion and loss of histone signatures that are characteristic of a repressive chromatin. Chromosome conformation capture assays indicated that –16.5 ECR physically interacts with the CCL2 proximal promoter after TNF-α stimulation. Taken together, these results suggest that the −16.5 ECR may play a critical role in the regulation of CCL2.

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Section: Discussioncontrasting

confidence: 47%

An Evolutionarily Conserved TNF-α–Responsive Enhancer in the Far Upstream Region of Human CCL2 Locus Influences Its Gene Expression

Bonello

Pham

Begum

et al. 2011

The Journal of Immunology

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“…In Vivo" Footprint in GATA HS1-DNA fragments from the HS1 region of the mouse GATA-1 gene have been shown previously to have enhancer activity, when linked to the GATA-1 promoter alone or in combination with HS2 and other GATA-1 regulatory elements, in transient transfections, and in transgenic assays (13)(14)(15)(16). The activity of HS1 is totally dependent on a strong GATA-1-binding site (14 -16) that appears to be occupied in vivo, as indicated by in vivo footprinting (14).…”

Section: An "mentioning

confidence: 99%

“…Constructs including the mouse GATA-1 promoter up to a DNase I-hypersensitive site lying at about Ϫ700 nts 1 (HS2) are expressed, at low efficiency, in adult hematopoietic cells in transgenic mice but not in yolk sac cells; however, constructs including an additional more upstream site (HS1) are much more efficient and are also active in primitive hematopoietic cells (12)(13)(14)(15)(16). GATAbinding sequences in HS1 and HS2 are essential for activity in a variety of constructs, suggesting GATA-1 auto-regulation (8 -10, 14 -16); however, a GATA-1 transgenic construct is active in mice lacking the endogenous GATA-1 gene, suggesting that other members of the GATA family of transcription factors (possibly GATA-2) may control GATA-1 transcription (13,16). As GATA-2 is expressed in a wider range of cell types than GATA-1, this implies that other regulatory elements are necessary for appropriate GATA-1 regulation.…”

mentioning

confidence: 99%

“…The regulation of the expression of GATA-1 itself has been the subject of many investigations (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Constructs including the mouse GATA-1 promoter up to a DNase I-hypersensitive site lying at about Ϫ700 nts 1 (HS2) are expressed, at low efficiency, in adult hematopoietic cells in transgenic mice but not in yolk sac cells; however, constructs including an additional more upstream site (HS1) are much more efficient and are also active in primitive hematopoietic cells (12)(13)(14)(15)(16).…”

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confidence: 99%

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Deletion of a Negatively Acting Sequence in a Chimeric GATA-1 Enhancer-Long Terminal Repeat Greatly Increases Retrovirally Mediated Erythroid Expression

Testa

Lotti

Cairns

et al. 2004

Journal of Biological Chemistry

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The locus control region of the ␤-globin gene cluster has been used previously to direct erythroid expression of globin genes from retroviral vectors for the purpose of gene therapy. Short erythroid regulatory elements represent a potentially valuable alternative to the locus control region. Among them, the GATA-1 enhancer HS2 was used to replace the retroviral enhancer within the 3 -long terminal repeat (LTR) of the retroviral vector SFCM, converting it into an erythroid-specific regulatory element. In this work, we have functionally studied an additional GATA-1 enhancer, HS1. HS1 participates in the transcriptional autoregulation of GATA-1 through an essential GATA-binding site that is footprinted in vivo. In this work we identified within HS1 a new in vivo footprinted region, and we showed that this sequence indeed binds a nuclear protein in vitro. Addition of HS1 to HS2 within the LTR of SFCM significantly improves the expression of a reporter gene. The deletion of the newly identified footprinted sequence in the retroviral construct further increases expression up to a level almost equal to that of the wild type retroviral LTR, without loss of erythroid specificity, suggesting that this sequence may act as a negative regulatory element. An improved vector backbone, M⌬N, allows even better expression from the new GATA cassette. These results suggest that substantial improvement of overall expression can be achieved by the combination of multiple changes in both regulatory elements and vectors.

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“…However, a number of regions critical for GATA-1 expression in erythroid cells and megakaryocytes have been identified by transgenic reporter experiments and targeted deletions in mice, and are summarized in figure 3. A genomic region that includes DNase 1 hypersensitive site lies approximately 3.5 kilobases upstream of the IE exon and can direct expression in primitive and definitive erythroid precursors and megakaryocytes, and has been referred to as an upstream enhancer (69)(70)(71). The large GATA-1 first intron contains exon IB and is important for definitive hematopoiesis, particularly in specifying expression in erythroid cells and megakaryocytes (72;73).…”

Section: Regulation Of the Gata-1 Locus In Mast Cellsmentioning

confidence: 99%

Mast cell transcriptional networks

Takemoto

Lee

Jegga

et al. 2008

Blood Cells, Molecules, and Diseases

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Unregulated activation of mast cells can contribute to the pathogenesis of inflammatory and allergic diseases, including asthma, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis (1;2). Absence of mast cells in animal models can lead to impairment in the innate immune response to parasites and bacterial infections (3)(4)(5). Aberrant clonal accumulation and proliferation of mast cells can result in a variety of diseases ranging from benign cutaneous mastocytosis to systemic mastocytosis or mast cell leukemia(6). Understanding mast cell differentiation provides important insights into mechanisms of lineage selection during hematopoiesis and can provide targets for new drug development to treat mast cell disorders,. In this review, we discuss controversies related to development, sites of origin,, and the transcriptional program of mast cells. KeywordsMast cells; transcription factors; GATA; PU.1; Mitf Origins of Mast CellsLike other granulocytes (neutrophils, eosinophils and basophils), mast cells are derived from hematopoietic stem cells in the marrow; however, they are unique with regard to the tissue compartments in which they traffic and reside. The gastrointestinal mucosa is the major compartment occupied by committed mast cell precursors in the mouse (7). Trafficking to these compartments is dependent on the expression of the alpha4 beta7 integrin and the chemokine receptor CXCR2.(8;9) Mast cell progenitors migrate to the connective tissue of the skin, lung, and the mucosa of other gastrointestinal tissues where they mature under the influence local Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Transplantation studies in mice indicate that mast cells are derived from hematopoietic stem cells of marrow (or spleen)(10;11). Studies using prospectively identified hematopoietic precursors have reported different precursor cells that give rise to the committed mast cell progenitor One study found that the committed mast cell progenitor (MCP) arose from an early multipotential progenitor (MPP) that is distinct from the common myeloid progenitor (12). However, using a similar strategy to prospectively isolate hematopoietic precursors from mouse marrow, another study found that the MCP was derived from either the common myeloid progenitor or the granulocyte-monocyte progenitor(13) (Figure 1). Plasticity may permit other committed progenitor cell populations to be "reprogrammed" into the mast cell lineage by altering the expression of selected transcription factors. Isolated common lymphoid precursors that are retrovirally-tranduced with the tr...

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A GATA Box in the GATA-1 Gene Hematopoietic Enhancer Is a Critical Element in the Network of GATA Factors and Sites That Regulate This Gene

Cited by 113 publications

References 36 publications

An Evolutionarily Conserved TNF-α–Responsive Enhancer in the Far Upstream Region of Human CCL2 Locus Influences Its Gene Expression

An Evolutionarily Conserved TNF-α–Responsive Enhancer in the Far Upstream Region of Human CCL2 Locus Influences Its Gene Expression

Deletion of a Negatively Acting Sequence in a Chimeric GATA-1 Enhancer-Long Terminal Repeat Greatly Increases Retrovirally Mediated Erythroid Expression

Mast cell transcriptional networks

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