REPRESSION OF GENES BY DNA METHYLATION DEPENDS ON CPG DENSITY AND PROMOTER STRENGTH - EVIDENCE FOR INVOLVEMENT OF A METHYL-CPG BINDING-PROTEIN
REPRESSION OF GENES BY DNA METHYLATION DEPENDS ON CPG DENSITY AND PROMOTER STRENGTH - EVIDENCE FOR INVOLVEMENT OF A METHYL-CPG BINDING-PROTEIN
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DOI：
10.1002/j.1460-2075.1992.tb05055.x
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发表时间：
1992-01-01
期刊：
影响因子：
11.4
通讯作者：
BIRD, A
中科院分区：
文献类型：
--
作者：
BOYES, J;BIRD, A
通过甲基-CpG结合蛋白MeCP-1(Boyes和Bird，1991)可以抑制高度甲基化基因的转录。在这里，我们研究了甲基化对低密度甲基CpG基因的影响。我们发现稀疏甲基化可以完全抑制转基因基因，但这种抑制可以被顺式基因中SV40增强子的存在完全克服。然而，高度甲基化的基因不能被增强子重新激活。体外研究表明，稀疏甲基化的基因与MeCP-1结合较弱，这种结合干扰了转录。在缺乏可用的MeCP-1的情况下，甲基化对转录的影响很小。根据这些和其他结果，我们认为稀疏甲基化的基因与MeCP-1形成一个不稳定的复合体，当启动子较弱时，它会阻止转录。这种复合体可以被强大的启动子破坏，从而允许甲基化基因转录。
Repression of transcription from densely methylated genes can be mediated by the methyl-CpG binding protein MeCP-1 (Boyes and Bird, 1991). Here we have investigated the effect of methylation on genes with a low density of methyl-CpG. We found that sparse methylation could repress transfected genes completely, but the inhibition was fully overcome by the presence in cis of an SV40 enhancer. Densely methylated genes, however, could not be reactivated by the enhancer. In vitro studies showed that the sparsely methylated genes bound weakly to MeCP-1 and that binding interfered with transcription. In the absence of available MeCP-1, methylation had minimal effects on transcription. From these and other results we propose that sparsely methylated genes form an unstable complex with MeCP-1 which prevents transcription when the promoter is weak. This complex can be disrupted by a strong promoter, thereby allowing the methylated gene to be transcribed.