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)-beta and TNF-alpha. 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-alpha and TNF-beta secretion by lymphocytes and macrophages, the transcriptional levels of the corresponding genes do not. The TNF-alpha gene is transcribed much more heavily than the TNF-beta gene in T lymphocytes, even though the TNF-beta mRNA is more abundant. Resting T lymphocytes and macrophages, which do not accumulate any TNF mRNA, nevertheless transcribe the TNF-alpha gene actively. On the other hand, the TNF-beta 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.
Jongeneel
C V
CV
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Shakhov
A N
AN
Nedospasov
S A
SA
Cerottini
J C
JC
D001483:Base Sequence; D002874:Chromosome Mapping; D006801:Humans; D008264:Macrophages / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha