Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the lysozyme gene in chicken macrophages is regulated by an enhancer located 2.7 kilobases upstream of the transcription start site. The organization of this enhancer was analyzed by in vitro assays (DNase I footprinting, dimethyl sulfate methylation protection, and band shift assays) and in vivo footprinting experiments. The results show that the enhancer contains four regions (I-IV) of protein-DNA interactions. First, transient gene transfer experiments demonstrate that region II contributes most to the enhancer function. This region contains a recognition site for the macrophage- and B cell-specific transcription factor PU.1, a member of the Ets transcription factor family. This site plays a major role in the enhancer since a mutation of this site abolishes enhancer activity. Second, in competition band shift experiments, we show that the only myeloid-specific complexes in regions I and II with nuclear factors are formed on the PU.1 recognition site by a member of the Ets transcription factor family. Third in in vivo footprinting experiments, the only sign of a protein-DNA interaction is a dimethyl sulfate-hyperreactive guanine 3'-adjacent to the PU.1 recognition site.
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PMID:Characterization of a myeloid-specific enhancer of the chicken lysozyme gene. Major role for an Ets transcription factor-binding site. 802 33

Cells of the mononuclear phagocyte lineage possess receptors for macrophage colony-stimulating factor (CSF-1) encoded by the c-fms protooncogene and respond to CSF-1 with increased survival, growth, differentiation, and reversible changes in function. The c-fms gene is itself a macrophage differentiation marker. In whole mount analyses of mRNA expression in embryos, c-fms is expressed at very high levels on placental trophoblasts. It is detectable on individual cells in the yolk sac around 8.5 to 9 days postcoitus, appears on isolated cells in the head of the embryo around 9.5 dpc, and appears on numerous cells throughout the embryo by day 10.5. The extent of c-fms expression is much greater than for other macrophage-specific genes including lysozyme and a macrophage-specific protein tyrosine phosphatase. Our studies of the cis-acting elements of the c-fms promoter have indicated a key role for collaboration between the macrophage-specific transcription factor, Pu.1, which functions in determining the site of transcription initiation, and other members of the Ets transcription factor family. This is emerging as a common pattern in macrophage-specific promoters. We have shown that two PU box elements alone can function as a macrophage-specific promoter. The activity of both the artificial promoter and the c-fms promoter is activated synergistically by coexpression of Pu.1 and another Ets factor, c-Ets-2. A 3.5kb c-fms exon 2 promoter (but not the 300bp proximal promoter) is also active in a wide diversity of tumor cell lines. The interesting exception is the melanoma cell line K1735, in which the promoter is completely shut down and expression of c-fms causes growth arrest and cell death. The activity of the exon 2 promoter in these nonmacrophages is at least as serum responsive as the classic serum-responsive promoter of the c-fos gene. It is further inducible in nonmacrophages by coexpression of the c-fms product. Unlike other CSF-1/c-fms-responsive promoters, the c-fms promoter is not responsive to activated Ras even when c-Ets-2 is coexpressed. In most lines, production of full length c-fms is prevented by a downstream intronic terminator, but in Lewis lung carcinoma, read-through does occur, and expression of both c-fms and other macrophage-specific genes such as lysozyme and urokinase becomes detectable in conditions of serum deprivation.
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PMID:Regulation of CSF-1 receptor expression. 898 63

Interferon regulatory factor-8 (IRF-8)/interferon consensus sequence-binding protein (ICSBP) is a transcription factor that controls myeloid-cell development. Microarray gene expression analysis of Irf-8-/- myeloid progenitor cells expressing an IRF-8/estrogen receptor chimera (which differentiate into macrophages after addition of estradiol) was used to identify 69 genes altered by IRF-8 during early differentiation (62 up-regulated and 7 down-regulated). Among them, 4 lysosomal/endosomal enzyme-related genes (cystatin C, cathepsin C, lysozyme, and prosaposin) did not require de novo protein synthesis for induction, suggesting that they were direct targets of IRF-8. We developed a reporter assay system employing a self-inactivating retrovirus and analyzed the cystatin C and cathepsin C promoters. We found that a unique cis element mediates IRF-8-induced activation of both promoters. Similar elements were also found in other IRF-8 target genes with a consensus sequence (GAAANN[N]GGAA) comprising a core IRF-binding motif and an Ets-binding motif; this sequence is similar but distinct from the previously reported Ets/IRF composite element. Chromatin immunoprecipitation assays demonstrated that IRF-8 and the PU.1 Ets transcription factor bind to this element in vivo. Collectively, these data indicate that IRF-8 stimulates transcription of target genes through a novel cis element to specify macrophage differentiation.
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PMID:Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. 1594 94

Myeloid elf-1-like factor (MEF) or Elf4 is an ETS protein known to regulate the basal expression of the anti-microbial peptides, lysozyme and human beta-defensin-2, in epithelial cells and activate the transcription of perforin in natural killer cells. The numerous target genes of MEF and its biological functions signify the importance of this Ets transcription factor. Here we show that MEF is modified by conjugation with SUMO-1/-2 (small ubiquitin-related modifier) both in mammalian cells and in Escherichia coli overexpressing human SUMO-1/-2. We identified by point mutation that lysine 657 of MEF is the site for sumoylation. This modification down-regulated MEF activity on lysozyme and perforin promoters, and decreased the lysozyme mRNA expression. Chromatin immuno-precipitation analysis revealed that SUMO-conjugation diminished the recruitment of MEF to the lysozyme promoter, which partly explains the down-regulation of MEF activity by SUMO. These findings contribute to our understanding of the regulation of the ETS factor MEF.
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PMID:SUMO down-regulates the activity of Elf4/myeloid Elf-1-like factor. 1690 44