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-2Kk molecules correlates 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-2Kk gene failed to activate transcription in H-2Kk-negative cells. Examination of the proteins interacting with the H-2Kk 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 beta 2-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/KBFI. In addition, it is shown that the same transcription factor is only present in mouse tissues expressing class I antigens.
Institut für Zellbiologie (Tumorforschung), Universität Essen, Federal Republic of Germany.
U
U
Henseling
W
W
Schmidt
H R
HR
Schöler
P
P
Gruss
A K
AK
Hatzopoulos
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics; D007942:Leukemia, Experimental / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000235:genetics; D015183:Restriction Mapping; D013489:Suppression, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000276:immunology
D006183:H-2 Antigens; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014157:Transcription Factors