Comparison of constitutive and inducible transcriptional enhancement mediated by κB-related sequences: Modulation of activity in B cells by human T-cell leukemia virus type I tax gene

The κB sequence (GGGACTTTCC) binds a factor, NF-κB, that is constitutively found in its functional, DNA binding form only in B lymphocytes. A factor with apparently indistinguishable sequence specificity can be induced in many other cell types, where it is used to regulate inducible gene expression. For example, κB-related sequences have been shown to be important for the transcription of a few inducible genes, such as the interleukin 2 receptor α-chain gene and the β-interferon gene. However, these genes are not constitutively active in B lymphocytes, suggesting that other regulatory mechanisms must play a role in determining the patterns of expression. We have investigated the constitutive and inducible transcriptional activity mediated by five κB-related sequence elements in two different cell types. We show that in S194 plasma cells the activity of each element correlates well with the relative affinity of B-cell-derived NF-κB for that element. This leads to significantly lower transcription enhancement by sites derived from the interleukin 2 receptor or T-cell receptor genes in S194 cells. However, in either EL-4 (T) cells or S194 cells, both lower-affinity sites can be significantly induced by the tax gene product of human T-cell leukemia virus type I, showing that NF-κB activity can be modulated even in a B-cell line that constitutively expresses this factor.