Functional analysis of the murine Emr1 promoter identifies a novel purine-rich regulatory motif required for high-level gene expression in macrophages

O’Reilly, Dawn; Addley, Mark; Quinn, Carmel M.; Macfarlane, Alison; Gordon, Siamon; McKnight, Andrew J.; Greaves, David R.

doi:10.1016/j.ygeno.2004.08.016

Cited by 19 publications

(22 citation statements)

References 39 publications

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“…To test the hypothesis that MafB directly regulates the F4/80 gene, we performed reporter assays using a 668-bp F4/80 promoter/luciferase construct that was cotransfected with a MafB expression vector (36,37). A well-conserved MARE half-site (CTTTCTGCTGAGTTGCCA [underlined letters are the consensus MARE half-site]) from Ϫ130 to Ϫ113 bp (37) was identified within the F4/80 promoter.…”

Section: Resultsmentioning

confidence: 99%

“…A recent report showed that 5Ј AT-rich MARE half-sites retain Maf binding site potency as strong as the classical palindromic MARE (49). Moreover, it was reported recently that a serial deletion study of that promoter revealed strong enhancer activity between Ϫ187 and Ϫ117 bp, which includes the predicted MARE element (37). It is therefore quite plausible that MafB binds to the F4/80 promoter at that site to stimulate F4/80 transcription in mature macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…The pGL3Basic-based 668-bp human F4/80 promoter luciferase construct was reported previously (37). A full-length MafB cDNA was subcloned into the pcDNA3.1ϩneo eukaryotic expression plasmid (Invitrogen).…”

Section: Construction Of the Mafb Targeting Vectormentioning

confidence: 99%

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MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

Moriguchi

Hamada

Morito

et al. 2006

Molecular and Cellular Biology

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MafB is a member of the large Maf family of transcription factors that share similar basic region/leucine zipper DNA binding motifs and N-terminal activation domains. Although it is well known that MafB is specifically expressed in glomerular epithelial cells (podocytes) and macrophages, characterization of the null mutant phenotype in these tissues has not been previously reported. To investigate suspected MafB functions in the kidney and in macrophages, we generated mafB/green fluorescent protein (GFP) knock-in null mutant mice. mafB homozygous mutants displayed renal dysgenesis with abnormal podocyte differentiation as well as tubular apoptosis. Interestingly, these kidney phenotypes were associated with diminished expression of several kidney disease-related genes. In hematopoietic cells, GFP fluorescence was observed in both Mac-1-and F4/80-expressing macrophages in the fetal liver. Interestingly, F4/80 expression in macrophages was suppressed in the homozygous mutant, although development of the Mac-1-positive macrophage population was unaffected. In primary cultures of fetal liver hematopoietic cells, MafB deficiency was found to dramatically suppress F4/80 expression in nonadherent macrophages, whereas the Mac-1-positive macrophage population developed normally. These results demonstrate that MafB is essential for podocyte differentiation, renal tubule survival, and F4/80 maturation in a distinct subpopulation of nonadherent mature macrophages.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

Moriguchi

Hamada

Morito

et al. 2006

Molecular and Cellular Biology

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202

255

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“…F4/80 promoter studies have examined the basis for cell-specific expression [17]. Functional analysis of the murine Emr1 (F4/80) promoter identified a novel purine-rich regulatory motif required for high-level gene expression in Mfs; PU.1 association is a prerequisite for Mf-specific expression.…”

Section: F4/80: Tissue Expressionmentioning

confidence: 99%

F4/80 and the related adhesion‐GPCRs

et al. 2011

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The F4/80 monoclonal antibody was first reported in this journal 30 years ago (Eur. J. Immunol. 1981. 11: 805–815). F4/80 has become a widely used marker for monocytes and many, but not all, tissue macrophages in the mouse. F4/80 is a member of the EGF‐TM7 family of leukocyte plasma membrane heptahelical molecules, which includes CD97 and EMR2. This Viewpoint summarises current knowledge of the expression, structure and functions of the EGF‐TM7 family, as part of a larger family of tissue adhesion‐GPCRs.

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“…Greaves and colleagues [23] recently demonstrated that the macrophage-specific expression of EMR1 in mice is regulated by a purine-rich sequence in the proximal promoter (positions -277 to -157), which contains nine potential PU.1-binding sites. In humans, this region is · Table 1.…”

Section: Emr1 Is Predominantly Transcribed In Eosinophilsmentioning

confidence: 99%

EMR1, the human homolog of F4/80, is an eosinophil‐specific receptor

et al. 2007

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The EGF-TM7 F4/80 is a defining marker of murine macrophage populations. Applying flow cytometric analysis using the newly generated mAb A10, and quantitative real-time PCR, we here report the surprising observation that the human ortholog of F4/80, EGFlike module containing mucin-like hormone receptor (EMR)1, is absent on mononuclear phagocytic cells including monocytes, macrophages, and myeloid dendritic cells. Unexpectedly, we found that EMR1 expression is restricted to eosinophilic granulocytes, where expression is overlapping with the eotaxin receptor CCR3 and the immunoglobulin-like lectin Siglec-8. Absence on other leukocytes, including basophils, implies that EMR1 is a highly specific marker for eosinophils in humans.

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Functional analysis of the murine Emr1 promoter identifies a novel purine-rich regulatory motif required for high-level gene expression in macrophages

Cited by 19 publications

References 39 publications

MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

MafB Is Essential for Renal Development and F4/80 Expression in Macrophages

F4/80 and the related adhesion‐GPCRs

EMR1, the human homolog of F4/80, is an eosinophil‐specific receptor

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