Transcriptional regulation of the mts1 gene in human lymphoma cells: the role of DNA-methylation

The transcription of the mts1 gene putatively involved in the control of tumor metastasis was studied in three human lymphoma cell lines: MOLT-4, CEM and Jurkat. The level of the mts1 gene transcription is high in MOLT-4 cells, lower in CEM cells and hardly detectable in Jurkat cells. This correlates with the hypomethylation of DNA in the first exon and the first intron of the mts1 gene in the analyzed culture cells. This area was also found to be undermethylated in human peripheral blood cells - macrophages, neutrophils and lymphocytes where the mts1 gene is highly expressed. 5-Azadeoxycytidine (AzadC) - an inhibitor of the eukaryotic DNA-methylase - significantly induces the expression of the mts1 gene in CEM and Jurkat cells and has little effect on mts1 gene transcription in MOLT-4 cells. The drug does not influence mts1 transcription in cultivated peripheral blood lymphocytes. These data indicate the possible involvement of the methylation of the first exon/first intron sequences in the transcriptional repression of the mts1 gene. The finding of two DNAaseI hypersensitivity sites (DHSs) mapped in the first intron of the mts1 gene supports this suggestion.