N-甲基脱氧腺苷指导四膜虫 DNA 中的核小体定位。
N-methyldeoxyadenosine directs nucleosome positioning in Tetrahymena DNA.
机构信息
The State Key Laboratory of Biocontrol, MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510060, China.
Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA.
出版信息
Genome Biol. 2018 Nov 19;19(1):200. doi: 10.1186/s13059-018-1573-3.
BACKGROUND
N-methyldeoxyadenosine (6mA or mdA) was shown more than 40 years ago in simple eukaryotes. Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited.
RESULTS
We use Tetrahymena thermophila as a model organism to examine the effects of 6mA on nucleosome positioning. Independent methods reveal the enrichment of 6mA near and after transcription start sites with a periodic pattern and anti-correlation relationship with the positions of nucleosomes. The distribution pattern can be recapitulated by in vitro nucleosome assembly on native Tetrahymena genomic DNA but not on DNA without 6mA. Model DNA containing artificially installed 6mA resists nucleosome assembling compared to unmodified DNA in vitro. Computational simulation indicates that 6mA increases dsDNA rigidity, which disfavors nucleosome wrapping. Knockout of a potential 6mA methyltransferase leads to a transcriptome-wide change of gene expression.
CONCLUSIONS
These findings uncover a mechanism by which DNA 6mA assists to shape the nucleosome positioning and potentially affects gene expression.
背景
N-甲基去氧腺苷（6mA 或 mdA）早在 40 多年前就在简单的真核生物中被发现。最近的研究表明，6mA 存在于更为普遍的真核生物中，甚至在脊椎动物中也存在。然而，其功能特征仍有限。
结果
我们使用嗜热四膜虫作为模型生物来研究 6mA 对核小体定位的影响。独立的方法显示，6mA 在转录起始位点附近和之后富集，呈现周期性模式，并与核小体位置呈反相关。这种分布模式可以通过在天然嗜热四膜虫基因组 DNA 上进行体外核小体组装来重现，但在没有 6mA 的 DNA 上则无法重现。与体外未修饰的 DNA 相比，含有人为安装的 6mA 的模型 DNA 更能抵抗核小体的组装。计算模拟表明，6mA 增加了双链 DNA 的刚性，不利于核小体包裹。潜在的 6mA 甲基转移酶的敲除导致了转录组范围内的基因表达变化。
结论
这些发现揭示了一种机制，即 DNA 6mA 有助于形成核小体定位，并可能影响基因表达。
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