Sp1/Sp3 and PU.1 Differentially Regulate β5Integrin Gene Expression in Macrophages and Osteoblasts

作者: Xu Feng , Steven L. Teitelbaum , Marisol E. Quiroz , Su-Li Cheng , Chung-Fang Lai

DOI: 10.1074/JBC.275.12.8331

关键词:

摘要: Murine osteoclast precursors and osteoblasts express the integrin alpha(v)beta(5), appearance of which on cell surface is controlled by beta(5), not alpha(v), subunit. Here, we show that a 173-base pair proximal region beta(5) promoter mediates basal transcription in macrophage (osteoclast precursor)-like osteoblast-like cells. DNase I footprinting reveal four regions (FP1-FP4) within region, protected nuclear extracts. In contrast, osteoblast extracts protect only FP1, FP2, FP3. FP3 bind Sp1 Sp3 from both FP4 does proteins but binds PU.1 macrophages. Transfection studies FP1 FP2 Sp1/Sp3 sites act as enhancers MC3T3-E1 (osteoblast-like) J774 (macrophage-like) lines, whereas site serves silencer. Mutation totally abolishes activity cells, with partial reduction Finally, demonstrate acts silencer cells plays no role Thus, three regulate gene expression macrophages each element exhibiting cell-type and/or activation-suppression specificity.

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