Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrosialin is a transmembrane glycoprotein that is highly expressed in macrophages. In the present studies, macrosialin mRNA levels are shown to be markedly up-regulated during macrophage differentiation of bone marrow progenitor cells in response to macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. To investigate the mechanisms responsible for regulation of macrosialin expression, we have isolated the macrosialin gene and performed an initial analysis of its transcriptional regulatory elements. The macrosialin promoter and 7.0 kilobase pairs of 5'-flanking information direct high levels of reporter gene activity in monocyte/macrophage-like cells, but little or no expression in nonmyeloid cells. This pattern of expression is dependent on regulatory elements located between -7.0 and -2.5 kilobase pairs from the transcriptional start site that exhibit strong enhancer activity in macrophages and repressor activity in nonmyeloid cells. Analysis of the proximal macrosialin promoter indicates that combinatorial interactions between at least four classes of transcriptional activators, including PU.1/Spi-1 and members of the AP-1 family are required for basal promoter function. PU.1/Spi-1 and c-Jun act synergistically to activate the macrosialin promoter in a nonmyeloid cell line, suggesting that combinatorial interactions between these proteins are involved in regulating macrosialin expression during macrophage differentiation.
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PMID:The macrosialin promoter directs high levels of transcriptional activity in macrophages dependent on combinatorial interactions between PU.1 and c-Jun. 947

The process through which multipotential hematopoietic cells commit to distinct lineages involves the induction of specific transcription factors. PU.1 (also known as Spi-1) and GATA-1 are transcription factors essential for the development of myeloid and erythroid lineages, respectively. Overexpression of PU.1 and GATA-1 can block differentiation in lineages in which they normally are down-regulated, indicating that not only positive but negative regulation of these factors plays a role in normal hematopoietic lineage development. Here we demonstrate that a region of the PU.1 Ets domain (the winged helix-turn-helix wing) interacts with the conserved carboxyl-terminal zinc finger of GATA-1 and GATA-2 and that GATA proteins inhibit PU.1 transactivation of critical myeloid target genes. We demonstrate further that GATA inhibits binding of PU.1 to c-Jun, a critical coactivator of PU.1 transactivation of myeloid promoters. Finally, PU.1 protein can inhibit both GATA-1 and GATA-2 transactivation function. Our results suggest that interactions between PU.1 and GATA proteins play a critical role in the decision of stem cells to commit to erythroid vs. myeloid lineages.
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PMID:Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1. 1041 39