Differential transcriptional control of the H-2K and H-2D loci of the major histocompatibility complex in fibrosarcoma cells.
In this study we demonstrate a differential transcription of H-2K and H-2D class-I genes in two different tumor cell clones; one is highly metastatic (IE-7) and the other is not metastatic (IC-9), both derived from the same fibrosarcoma, T-10, induced in an (H-2b x H-2k)F1 mouse. The expression of the two parental H-2K alleles is transcriptionally suppressed in both of these clones. In addition the IC-9 clone does not transcribe also the H-2Dk allele. Our data rule out the possibility that this suppression results from enhanced RNA degradation, impaired polyadenylation, DNA rearrangement, or changes in DNA methylation within these genes. Interferons (IFN) are known to enhance MHC expression by acting on a consensus IFN responsive element present in the promoter region of MHC genes. However, IFN-gamma, which is the most potent IFN in this respect, failed to activate the expression of the silent MHC genes in our cells. This finding may reflect a defect within the promoter region of these genes or changes in their chromatin structure.
Aboud
M
M
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Amitai
H
H
Huleihel
M
M
Har-vardi
I
I
Gopas
J
J
Segal
S
S
D000483:Alleles; D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D002999:Clone Cells; D005354:Fibrosarcoma / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D015321:Gene Rearrangement; D005805:Genes, MHC Class I / Q000235:genetics*; D006183:H-2 Antigens / Q000235:genetics*; D007370:Interferon Type I / Q000494:pharmacology; D008745:Methylation; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D013489:Suppression, Genetic / Q000235:genetics; D014158:Transcription, Genetic
D006183:H-2 Antigens; D007370:Interferon Type I; D012333:RNA, Messenger; D001374:Azacitidine