Molecular control of tissue‐specific expression at the mouse TNF locus

We have examined the patterns of mRNA accumulation and transcription of the tandemly linked genes for tumor necrosis factor (TNF)‐β and TNF‐α. In spite of their tandem arrangement and close linkage, the two TNF genes utilize separate promoters. Our results show that, while levels of mRNA correlate with patterns of TNF‐α and TNF‐β secretion by lymphocytes and macrophages, the transcriptional levels of the corresponding genes do not. The TNF‐α gene is transcribed much more heavily than the TNF‐β gene in T lymphocytes, even though the TNF‐β mRNA is more abundant. Resting T lymphocytes and macrophages, which do not accumulate any TNF mRNA, nevertheless transcribe the TNF‐α gene actively. On the other hand, the TNF‐β gene is transcriptionally silent in macrophages. Our results are consistent with a model where tissue specificity is controlled transcriptionally, whereas post‐transcriptional events differentially control mRNA abundance.