ASYMMETRIC REDUNDANCY IN CD4 SILENCER FUNCTION

We and others have defined a transcriptional silencer critical for the proper expression of the CD4 gene at all stages of T cell development . In this report, we use biochemical techniques to identify three diff erent factor-binding sites within the CD4 silencer, denoted sites I, I I, and III. Using transgenic analyses, we determine that although all three factor-binding sites are important for silencer activity, there is significant redundancy in that the presence of either site II alone , or the combination of sites I and III permits silencer function. Thu s, our data indicate that the mechanism of function of the CD4 silence r is extremely complex. Further biochemical analyses indicate that the factor binding to site II has the same sequence specificity as a fact or binding to an E box site in the CD4 enhancer; thus, a member of the bHLH factor family may be important in mediating silencer function.