Kirillov A, Kistler B, Mostoslavsky R, Cedar H, Wirth T, Bergman Y
The Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Nat Genet. 1996 Aug;13(4):435-41. doi: 10.1038/ng0895-435.
The immunoglobulin kappa gene is specifically demethylated during B-cell maturation in a process which utilizes discrete cis-acting modules such as the intronic kappa enhancer element and the matrix attachment region (MAR). While any MAR sequence is sufficient for this reaction, mutation analysis indicates that tissue specificity is mediated by kappaB binding sequences within the kappa intronic enhancer. The plasmacytoma cell line S107 lacks kappaB binding activity and fails to demethylate the kappa locus. However, B-cell specific demethylation is restored by the introduction of an active kappaB binding protein gene relB. This represents the first demonstration of a trans-acting factor involved in cell-type-specific demethylation, and suggests that the same protein-DNA recognition system used for transcription may also contribute to the earlier developmental events that bring about activation of the kappa locus.
免疫球蛋白κ基因在B细胞成熟过程中会发生特异性去甲基化，这一过程利用了离散的顺式作用模块，如内含子κ增强子元件和基质附着区域（MAR）。虽然任何MAR序列都足以引发此反应，但突变分析表明，组织特异性是由κ内含子增强子内的κB结合序列介导的。浆细胞瘤细胞系S107缺乏κB结合活性，无法使κ基因座去甲基化。然而，通过引入活性κB结合蛋白基因relB可恢复B细胞特异性去甲基化。这首次证明了一种参与细胞类型特异性去甲基化的反式作用因子，并表明用于转录的相同蛋白质 - DNA识别系统也可能有助于引发κ基因座激活的早期发育事件。
