C/EBPalpha functionally and physically interacts with GABP to activate the human myeloid IgA Fc receptor (Fc alphaR, CD89) gene promoter.
Human Fcalpha receptor (Fc alphaR; CD89), the receptor for the crystallizable fragment (Fc) of immunoglobulin 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/EBPalpha) (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 (GABPalpha), an Ets-related factor, and GABPbeta, a Notch-related protein. Cotransfection of GABP increased FCAR promoter activity 3.7-fold through the Ets-binding site. GABP and C/EBPalpha synergistically activated the FCAR promoter 280-fold. Consistent with these observations, in vitro binding analyses revealed a physical interaction between the GABPalpha subunit and C/EBPalpha. This is the first report demonstrating both physical and functional interactions between GABP and C/EBPalpha and will provide new insights into the molecular basis of myeloid gene expression.
Shimokawa
Toshibumi
T
Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, Itabashi-ku, Tokyo, Japan.
Ra
Chisei
C
D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D019070:Cell Lineage; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011961:Receptors, Fc / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020298:U937 Cells
D015703:Antigens, CD; D022763:CCAAT-Enhancer-Binding Protein-alpha; C036832:Fc(alpha) receptor; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins; D004247:DNA