Investigations into the regulation of gene families such as the albumin/AFP, globin, and amylase loci have provided important insights into mechanisms of cellular differentiation and developmental control. The regulation of human receptors for the Fc portion of IgG exemplifies another system with tight cellspecific constraints. Responsible for mediating a wide variety of immunologic responses, these proteins are encoded by a structurally related group of genes; the locus is located on the long arm of chromosome 1, and arose relatively recently in evolution by duplication of a single gene. Although distinctly structurally similar, the expression of the various Fc receptors is nonetheless highly cell-specific, contributing in part to their substantial functional diversity. This study proposes to define these cis- and trans-acting factors responsible for the regulation of this unusual locus. An in vitro model mimicking the cell-type specificity of the native IIB and IIC genes will be constructed using continuous cell lines. Functional mapping of the cis-regulatory regions using deletion and mutational analysis will be undertaken, and protein interactions will be defined by DNAse hypersensitivity, footprinting, and gel retardation analysis. Finally, those proteins interacting with these regulatory regions will be isolated and purified. Such studies will provide important insights into the regulation of this interesting and unusual locus, and may also offer insights into unique transcriptional regulators vital to hematopoietic growth and differentiation.
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