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首页> 外文期刊>Journal of Molecular Biology >Mouse Dnmt3a preferentially methylates linker DNA and is inhibited by histone H1.
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Mouse Dnmt3a preferentially methylates linker DNA and is inhibited by histone H1.

机译：小鼠Dnmt3a优先甲基化连接子DNA，并被组蛋白H1抑制。

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摘要

In mammals, DNA methylation is crucial for embryonic development and germ cell differentiation. The DNA methylation patterns are created by de novo-type DNA methyltransferases (Dnmts) 3a and 3b. Dnmt3a is crucial for global methylation, including that of imprinted genes in germ cells. In eukaryotic nuclei, genomic DNA is packaged into multinucleosomes with linker histone H1, which binds to core nucleosomes, simultaneously making contacts in the linker DNA that separates adjacent nucleosomes. In the present study, we prepared oligonucleosomes from HeLa nuclei with or without linker histone H1 and used them as a substrate for Dnmt3a. Removal of histone H1 enhanced the DNA methylation activity. Furthermore, Dnmt3a preferentially methylated the linker between the two nucleosome core regions of reconstituted dinucleosomes, and the binding of histone H1 inhibited the DNA methylation activity of Dnmt3a towards the linker DNA. Since an identical amount of histone H1 did not inhibit the activity towards naked DNA, the inhibitory effect of histone H1 was not on the Dnmt3a catalytic activity but on its preferential location in the linker DNA of the dinucleosomes. The central globular domain and C-terminal tail of the histone H1 molecule were indispensable for inhibition of the DNA methylation activity of Dnmt3a. We propose that the binding and release of histone H1 from the linker portion of chromatin may regulate the local DNA methylation of the genome by Dnmt3a, which is expressed ubiquitously in somatic cells in vivo.
机译：在哺乳动物中，DNA甲基化对于胚胎发育和生殖细胞分化至关重要。 DNA甲基化模式是由从头型DNA甲基转移酶（Dnmts）3a和3b创建的。 Dnmt3a对于全球甲基化至关重要，包括生殖细胞中印迹基因的甲基化。在真核中，基因组DNA被包装到带有连接组蛋白H1的多核小体中，该组蛋白H1与核心核小体结合，同时在分离相邻核小体的连接子DNA中形成接触。在本研究中，我们从具有或没有接头组蛋白H1的HeLa核中制备了寡核小体，并将其用作Dnmt3a的底物。去除组蛋白H1增强了DNA甲基化活性。此外，Dnmt3a优先甲基化重建的双核小体的两个核小体核心区域之间的接头，组蛋白H1的结合抑制了Dnmt3a对接头DNA的DNA甲基化活性。由于相同量的组蛋白H1不会抑制裸DNA的活性，因此组蛋白H1的抑制作用不是对Dnmt3a催化活性的抑制作用，而是其在二核小体的连接子DNA中的优先位置。组蛋白H1分子的中心球状结构域和C末端尾部对于抑制Dnmt3a的DNA甲基化活性必不可少。我们建议从染色质的连接器部分的组蛋白H1的绑定和释放可能通过Dnmt3a调节基因组的局部DNA甲基化，Dnmt3a在体内的体细胞中普遍表达。

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