Chromatin structure of the lymphocyte Fc epsilon receptor gene (CD23): identification of an upstream transcriptional enhancer

The low-affinity receptor for IgE of lymphocytes, Fc epsilonRII or CD23, is likely to play pivotal roles in normal B cell differentiation, EBV induced B cell immortalization and regulation of the IgE response to allergens and to parasitic infection. We have studied the expression of CD23 mRNA in several cell contexts. In EBV-infected Burkitt lymphoma cells, we have confirmed that high levels of expression are determined largely at the level of gene transcription by performing nuclear run-on transcription analyses and stability determinations of CD23 mRNA in actinomycin D chase experiments. In an effort to define the complexity of the potential modes of activation of CD23 in various cell contexts, we have studied the chromatin structure of the gene as determined by the pattern and distribution of DNasel hypersensitive sites in CD23. We have found that, unlike the results obtained in many analogous systems, there is no distinct pattern of hypersensitive sites that uniquely correlates with high levels of CD23 transcription in various B lineage cell lines. Instead, we found a complex pattern that suggests that CD23 expression is regulated by trans-acting regulatory factors whose activity is dependent upon the stage of cellular differentiation as well as the cell lineage. By determining whether the DNA encompassing these hypersensitive sites contains transcriptional enhancer activity, we discovered a novel enhancer that functions in an EBV-dependent fashion and encompasses a 384-bp segment that lies 3.7 kb upstream from the transcription start site.