A TRANSCRIPTION FACTOR INTERACTING WITH THE CLASS-I GENE ENHANCER IS INACTIVE IN TUMORIGENIC CELL-LINES WHICH SUPPRESS MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENES

AKR leukemias display different amounts of major histocompatibility complex class I antigens on the cell surface. The absence of H-2K(k) molecules correlated with the ability of these cell lines to form tumors in vivo as well as to escape lysis by cytotoxic T lymphocytes in vitro. In this report it is shown that the 5' regulatory area of the H-2K(k) gene failed to activate transcription in H-2K(k)-negative cells. Examination of the proteins interacting with the H-2K(k) enhancer in expressing and nonexpressing cells revealed clear differences. In particular, the level of a nuclear protein interacting at position -166 was greatly reduced in the negative cell lines. A transcription factor, known as H2TF1 or KBF1, has been shown previously to interact with this binding site and to be essential for the expression of certain class I genes as well as the expression of β2-microglobulin. These results demonstrate that the molecular mechanism of class I gene suppression in malignant tumor cells is at the level of transcription and is most probably modulated by H2TF1/KBF1. In addition, it is shown that the same transcription factor is only present in mouse tissues expressing class I antigens.