Carotti D, Funiciello S, Lavia P, Caiafa P, Strom R
Department of Biochemical Sciences A. Rossi Fanelli, University of Rome La Sapienza, Italy.
Biochemistry. 1996 Sep 10;35(36):11660-7. doi: 10.1021/bi9606051.
We have characterized the inhibition exerted by histone H1 on the activity of human placenta DNA (cytosine-5-)-methyltransferase. Our experiments demonstrate that the extent of inhibition depends on the DNA base composition, AT-rich substrates being more severely affected than GC-rich substrates and CpG-rich islands. With bacterial SssI methylase, the effect is completely reversed since its activity on AT-rich substrates undergoes a 4-5-fold stimulation upon the addition of H1. Poly(L-lysine) mimicks H1 effects, suggesting an essential role of lysine residues in both the inhibitory and stimulatory effects of H1. By comparison of the different behaviors of the two enzymes, the inhibitory effect over the eukaryotic enzyme might be accounted for by hypothesizing a competition between minor groove-binding motifs (SPKK-like) present in placenta methylase as well as in histone H1.
我们已经对组蛋白H1对人胎盘DNA(胞嘧啶-5-)-甲基转移酶活性的抑制作用进行了表征。我们的实验表明,抑制程度取决于DNA碱基组成,富含AT的底物比富含GC的底物和富含CpG的岛受到的影响更严重。对于细菌SssI甲基转移酶,这种影响完全相反,因为在添加H1后,其对富含AT底物的活性会受到4至5倍的刺激。聚(L-赖氨酸)模拟了H1的作用,表明赖氨酸残基在H1的抑制和刺激作用中都起着重要作用。通过比较这两种酶的不同行为,对真核酶的抑制作用可能是由于假设胎盘甲基转移酶和组蛋白H1中存在的小沟结合基序(类SPKK)之间存在竞争。