CD4 gene transcription is transiently repressed during differentiation of myeloid cells to macrophage-like cells

The CD4 glycoprotein, which serves as receptor for human immunodeficiency virus (HIV), is expressed in several types of cells of hematopoietic origin, including T lymphocytes and monocytes. Triggering differentiation of peripheral blood monocytes, monocytic U-937 or promyelocytic HL-60 precursor cells to macrophage-like cells by phorbol ester treatment transiently induced both a rapid reduction in surface CD4, demonstrated by flow-cytometry analysis, and a gradual loss of CD4 mRNA, revealed by Northern-blot analysis. Experiments in HL-60 cells to determine the cause of the observed decay in CD4 mRNA levels suggested that the half-life of CD4 transcripts did not diminish but increased after phorbol ester stimulation. Direct measurement of CD4 gene transcription by run-on analysis indicated that the rate of synthesis of new CD4 mRNA molecules was reduced approximately 10-fold after phorbol ester stimulation, whereas the rate of synthesis of c-fos mRNA resulted in a 2.5-fold increase. These data suggest that phorbol ester treatment specifically reduces CD4 mRNA levels by repressing CD4 gene transcription. These findings may be relevant to understand the regulation of CD4 gene expression during differentiation.