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

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Abstract
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.