Tulchinsky E, Grigorian M, Tkatch T, Georgiev G, Lukanidin E
Danish Cancer Society, Department of Molecular Cancer Biology, Copenhagen.
Biochim Biophys Acta. 1995 Apr 4;1261(2):243-8. doi: 10.1016/0167-4781(95)00013-7.
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 mts 1 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.
MOLT-4、CEM和Jurkat中推测参与肿瘤转移控制的mts1基因转录进行了研究。mts1基因转录水平在MOLT-4细胞中较高，在CEM细胞中较低，而在Jurkat细胞中几乎检测不到。这与所分析培养细胞中mts1基因第一个外显子和第一个内含子中DNA的低甲基化相关。在人类外周血细胞——巨噬细胞、中性粒细胞和淋巴细胞中，mts1基因高度表达，该区域也被发现存在低甲基化。5-氮杂脱氧胞苷（AzadC）——一种真核DNA甲基化酶抑制剂——能显著诱导CEM和Jurkat细胞中mts1基因的表达，而对MOLT-4细胞中mts1基因转录影响很小。该药物对培养的外周血淋巴细胞中mts1转录无影响。这些数据表明第一个外显子/第一个内含子序列的甲基化可能参与了mts1基因的转录抑制。在mts1基因第一个内含子中定位到两个DNA酶I超敏位点（DHSs）这一发现支持了这一推测。
