The research plan proposes to study the mechanism of myeloid-specific regulation of the igG Fc receptor type I (FcgammaRI) gene. FcgammaRI is expressed exclusively by monocytes, macrophages and cells of the granulocytic series. The gene is also developmentally regulated during granulocyte differentiation. The proposed research will investigate the transcriptional regulation of the FcgammaRI gene in order to identify a protein which is critical for myelopoiesis. Preliminary work by the candidate has shown that fcgammaRI is transcriptionally regulated by interferon-gamma (IFN-gamma). A region of the gene mediating IFN-gamma-responsiveness has been identified by reported gene assays. The research plan proposes to study the promoter region of FcgammaRI further in order to characterize a region that is responsible for myeloid-specific expression. Various FcgammaRI promoter fragments will be subjected to reporter gene assays in myeloid and non- myeloid leukemia cell lines in order to identify a region conferring myeloid-specificity. This region will be analyzed further by DNase I footprinting. Myeloid proteins interacting specifically with footprinted DNA regions will be studied by gel retardation and UV cross-linking analyses. A potential myeloid-specific transcription factor will be cloned by probing a lambdagt11 cDNA library.
