Ammerpohl O, Schmitz A, Steinm ller L, Renkawitz R
Genetisches Institut, Justus-Liebig-Universität, Heinrich-Buff-Ring 58-62, D-35392 Giessen, Germany.
Nucleic Acids Res. 1998 Dec 1;26(23):5256-60. doi: 10.1093/nar/26.23.5256.
In many cases, gene repression mediated by CpG methylation has been demonstrated. Two different mechanisms have been postulated to explain the repressive effect of methylated CpG DNA: establishment of a repressive chromatin configuration and inhibition of DNA binding of transactivating factors. Using the M-lysozyme gene, we analyzed gene expression, CpG demethylation and the in vivo formation of enhancer/protein complexes after inducing demethylation or inhibiting histone deacetylases. We show that trans-cription of a methylated and silent mouse M-lysozyme gene can be induced upon the inhibition of histone deacetylases in the absence of demethylation or in vivo transactivating factor binding to the enhancer. In contrast, DNA demethylation induces both gene activity as well as enhancer complex formation. Therefore, both mechanisms play a role in lysozyme gene repression mediated by methylated DNA: (i) the enhancer cannot be loaded with transacting factors; and (ii) histone deacetylation inhibits transcription.
在许多情况下，已证实存在由CpG甲基化介导的基因抑制。人们推测了两种不同机制来解释甲基化CpG DNA的抑制作用：建立抑制性染色质构型以及抑制反式激活因子与DNA的结合。利用M-溶菌酶基因，我们在诱导去甲基化或抑制组蛋白脱乙酰酶后，分析了基因表达、CpG去甲基化以及增强子/蛋白质复合物的体内形成情况。我们发现，在不存在去甲基化或体内反式激活因子与增强子结合的情况下，抑制组蛋白脱乙酰酶可诱导甲基化且沉默的小鼠M-溶菌酶基因转录。相比之下，DNA去甲基化可诱导基因活性以及增强子复合物形成。因此，这两种机制在甲基化DNA介导的溶菌酶基因抑制中均发挥作用：（i）增强子无法结合反式作用因子；（ii）组蛋白去乙酰化抑制转录。
