Extinction of expression of the genes encoding haematopoietic cell-restricted transcription factors in T-lymphoma x fibroblast cell hybrids

We previously reported that expression of the T-cell receptor (TCR) alpha a nd lck genes is extinguished in hybrids between mouse T-lymphoma EL4 cells and mouse fibroblast B82 cells. In the present study, we found that the act ivities of the TCR alpha minimum enhancer and the lck promoter monitored by the luciferase or chloramphenicol acetyltransferase (CAT) assays were mark edly inhibited in the hybrids. Expression of the TCF-1, LEF-1, GATA-3, Ikar os, c-myb and Fli-1 genes, which encode the haematopoietic cell-restricted transcription factors that appear to be responsible for the activities of t he enhancer and the promoter, was fully extinguished or markedly suppressed in the hybrids. On the other hand, expression of the transcription factor genes observed in both parental cells, such as the AML1 and c-ets-1 genes, and that of the genes encoding ubiquitously expressed transcription factors , such as the E2A, CREB and c-ets-2 genes, was not significantly suppressed in the hybrids. These results suggest that the genes encoding haematopoiet ic cell-restricted transcription factors are targets for negative regulatio n in fibroblastic background and that the repression of these genes may con sequently lead to suppression of the promoter and/or enhancer activities of several T-cell-specific structural genes in T-lymphoma x fibroblast cell h ybrids.