Structure of the rat platelet factor 4 gene: a marker for megakaryocyte differentiation.

Doi, Takefumi; Greenberg, Sheryl M.; Rosenberg, Robert D.

doi:10.1128/mcb.7.2.898

Cited by 95 publications

(47 citation statements)

References 48 publications

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“…This fourth exon of the IP-10 gene almost exclusively encodes this 3' untranslated region and may play a role in the inducible transient expression of the IP-10 mRNA. In contrast, both rat (11) and human (28) PF4 genes contain short 3' untranslated regions and are constitutively expressed in platelets. This is consistent with the hypothesis that the 3' untranslated region of the IP-10 gene is responsible, at least in part, for its regulation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genomic characterization of a gamma-interferon-inducible gene (IP-10) and identification of an interferon-inducible hypersensitive site.

Luster¹,

Ravetch²

1987

Mol. Cell. Biol.

139

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The genomic organization of a gamma-interferon-inducible gene, IP-1O, reveals three introns that interrupt the transcribed sequence into four functional domains. Comparison of the intron-exon structure of this gene to the gene for an homologous chemotactic platelet protein, platelet factor 4, establishes that both genes are interrupted in precisely the same positions within homologous codons; this demonstrates that they belong to a gene family that evolved from a common ancestor. IP-IO and PF4 are two members of a newly described gene family that is likely to include the homologous chemotactic and mitogenic platelet basic proteins (connective tissue-activating protein Ill and P-thromboglobulin), the transformation-related protein 9E3, and 310c, a mitogen-stimulated leukocyte protein. A DNase I-hypersensitive site has been found in responsive cells in a region upstream of the RNA initiation site. This hypersensitive site is induced by gamma interferon and thus provides a structural basis for the transcriptional activation seen for this gene by gamma interferon.

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Section: Discussionmentioning

confidence: 99%

“…Recently, the genomic organization of a member of this family of homologous cytokines, PF4, has been determined from the rat genome (11). A comparison of the rat PF4 cDNA sequence with its genomic sequence has revealed that the PF4 gene is organized into three exons and two introns.…”

Section: *Corresponding Authormentioning

confidence: 99%

Genomic characterization of a gamma-interferon-inducible gene (IP-10) and identification of an interferon-inducible hypersensitive site.

Luster¹,

Ravetch²

1987

Mol. Cell. Biol.

139

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“…Experiments to determine the arrangement of LD78 genes on human chromosomes are in progress in our laboratory. Genomic organizations of several other members of the new cytokine superfamily have recently been determined (6,13,15,18,22,28,36), and their structures are schematically summarized in Fig. 8.…”

Section: Discussionmentioning

confidence: 99%

Structures of human genes coding for cytokine LD78 and their expression.

Nakao¹,

Nomiyama²,

Shimada³

1990

Mol. Cell. Biol.

113

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LD78 is a member of a newly identified superfamily of small inducible proteins involved in inflammatory responses, wound healing, and tumorigenesis. Southern blot analysis of the EcoRI-digested human genomic DNAs, using previously isolated LD78 cDNA as a probe, showed that in each individual there are 4.2-and 4.8-kilobase-pair (kb) fragments and that some have an additional 6.5-kb fragment. The 4.2-kb fragment contained genomic DNA sequences corresponding to the LD78 cDNA and was named the LD78a gene. The 4.8-kb fragment contained similar sequences, showing 94% homology to the LD78a gene, and was named the LD78j gene. The LD78a gene was present in a single or a few copies per haploid genome, whereas the copy number of the LD78, gene and of the 6.5-kb fragment hybridizable to LD78 cDNA varied among the samples tested. Treatment of human myeloid cell lines HL-60 and U937 with phorbol 12-myristate 13-acetate (PMA) increased within 2 h cellular levels of the RNA hybridizable to LD78 cDNA. The human glioma cell line U105MG and primary culture of human fibroblasts also expressed the hybridizable RNA in response to PMA. Addition of cycloheximide had no apparent effect on this response in U937 cells and inhibited the response in fibroblasts, whereas it stimulated the response in HL-60 and U1O5MG cells. mRNA phenotyping experiments revealed that the LD78a and LD78I8 genes were both transcribed in PMA-stimulated U937 cells.We formerly isolated a cDNA clone, named pLD78, from a cDNA library constructed on the poly(A)+ RNA of human tonsillar lymphocytes stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutinin, using a differential screening procedure (33). Sequence analysis of the pLD78 cDNA revealed that it codes for a protein of 92 amino acid residues, including a putative leader sequence. To obtain information on the function of this LD78 protein, we made a computer search of nucleotide and protein sequence data bases and found that it has significant similarity to small inducible mammalian proteins forming a new cytokine superfamily (for reviews, see references 4, 34, and 49). Although the exact functions of the members of this cytokine superfamily are unknown, a monocyte-derived neutrophil chemotactic factor, now called interleukin-8 (IL-8), is one of the best-characterized proteins (21).Among the members of the superfamily, LD78 has 75% sequence similarity with murine macrophage inflammatory protein la (MIP-lot) (10), also called murine L2G25B (20). Accordingly, we presume that LD78 is a human counterpart of murine MIP-la. Murine MIP-la has already been demonstrated to have inflammatory and chemokinetic properties (11,50). Recently, we found that high levels of LD78 gene transcripts are present in acute nonlymphotic as well as lymphotic leukemic cells; hence, LD78 is also probably involved in the neoplastic transformation of hematopoietic cells (51).We have now obtained evidence for at least three different LD78-like genes in the human genome. Among them, we isolated and characterized two highly ho...

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“…Platelet factor 4 (PF4) is expressed exclusively in megakaryocytes and platelets. 1 Because the PF4 gene is activated during the late stages of megakaryocytopoiesis, it is useful as a specific marker of megakaryocytic differentiation. 2 We have previously sequenced and characterized the rat PF4 promoter.…”

Section: Introductionmentioning

confidence: 99%

Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene

Okada

Nagai

Sato

et al. 2003

Blood

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Platelet factor 4 (PF4) is expressed during megakaryocytic differentiation. We previously reported that GATA-1 and ETS-1 regulate the rat PF4 promoter and transactivate the PF4 gene. For the present study, we investigated the regulatory elements and their transcription factors responsible for the lineage-specific expression of the PF4 gene. The promoter activities of deletion constructs were evaluated, and a novel regulatory element termed TME (tandem repeat of MEIS1 binding element) (؊219 to ؊182) was defined. Binding proteins to TME were strongly detected in HEL nuclear extracts by electrophoresis mobility shift assay (EMSA), and they were purified by DNA affinity chromatography. By performing Western blottings and supershift assays, the binding proteins were identified as homeodomain proteins, MEIS1, PBX1B, and PBX2. These factors are expressed in megakaryocytes differentiated from CD34 ؉ cells in human cord blood. MEIS1 and PBXs bind to the TME as MEIS1/PBX complexes and activate the PF4 promoter. In nonmegakaryocytic HepG2 cells, GATA-1 and ETS-1 activate the PF4 promoter approximately 10-fold. Surprisingly, we found that additional expression of both MEIS1 and PBX2 multiplied this major activation another 2-fold. This activation was not observed when MEIS1 binding sites in the TME were disrupted. Furthermore, inhibition of the binding of endogenous MEIS1/ PBX complexes to the TME decreased the promoter activity by almost one half, in megakaryocytic HEL cells.

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Structure of the rat platelet factor 4 gene: a marker for megakaryocyte differentiation.

Cited by 95 publications

References 48 publications

Genomic characterization of a gamma-interferon-inducible gene (IP-10) and identification of an interferon-inducible hypersensitive site.

Genomic characterization of a gamma-interferon-inducible gene (IP-10) and identification of an interferon-inducible hypersensitive site.

Structures of human genes coding for cytokine LD78 and their expression.

Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene

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