C/EBPα functionally and physically interacts with GABP to activate the human myeloid IgA Fc receptor (FcαR, CD89) gene promoter

Human Fc alpha receptor (Fc alpha R; CD89), the receptor foe the crystallizable fragment (Fc) of immunbglobulin A (IgA), is expressed exclusively in myeloid cells, including granulocytes and monocytes/macrophages, and is considered to define a crucial role of these cells in immune and inflammatory responses. A 259-base pair fragment of the FCAR promoter is sufficient to direct myeloid expression of a reporter, gene and contains functionally important binding sites for CCAAT/enhancer-binding protein alpha (C/ EbP alpha) (CE1, CE2, and CE3) and an unidentified Ets-like nuclear protein. Here, we show that the Ets-binding site is bound by a heterodimer composed of GA-binding protein alpha (GABP alpha), an Ets-related. factor, and GABP beta, a Notch-related protein. Cotransfection of GABP increased FCAR promoter activity 3.7-fold through, the Ets-binding site. GABP and C/EBP alpha synergistically activated the FCAR promoter 280-fold. Consistent with these observations, in vitro binding analyses revealed a physical interaction between the GASP alpha subunit and C/EBP alpha. This is the first report demonstrating both physical and functional interactions between GABP and C/EBP alpha, and will provide new insights into the molecular basis of myeloid gene expression.