N(4)-acetyldeoxycytosine DNA modification marks euchromatin regions in Arabidopsis thaliana.

N(4)-acetyldeoxycytosine DNA modification marks euchromatin regions in Arabidopsis thaliana.
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DOI:
10.1186/s13059-021-02578-7
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发表时间:
2022-01-03
期刊:
影响因子:
12.3
通讯作者:
Wu Y
Wu Y
中科院分区:
生物学1区
文献类型:
--
作者:
Wang S;Xie H;Mao F;Wang H;Wang S;Chen Z;Zhang Y;Xu Z;Xing J;Cui Z;Gao X;Jin H;Hua J;Xiong B;Wu Y

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携带重要表观遗传信息的化学修饰碱基的直接类似物,如5-甲基胞嘧啶(m5 C)/5-甲基脱氧胞嘧啶(5 mC),5-羟甲基胞嘧啶(hm 5C)/5-羟甲基脱氧胞嘧啶(5 hmC)和N6-甲基腺苷(m6 A)/N6-甲基脱氧腺苷(6 mA),分别在RNA和DNA中检测到。修饰的碱基N4-乙酰胞嘧啶(ac 4C)在RNA中得到了很好的研究,但其在细胞DNA中的存在和表观遗传作用尚未被探索。在这里,我们证明了存在的N4-乙酰脱氧胞嘧啶(4acC)在拟南芥基因组DNA的多种检测方法。4acC修饰的全基因组分析表明,4acC峰主要分布在常染色质区域,并存在于近一半的表达蛋白编码基因中。4acC主要位于转录起始位点周围,与基因表达水平正相关。5 mC的不平衡不会直接影响4acC的修饰。我们还表征了4acC与5 mC和组蛋白修饰的协会,合作调节基因表达。此外,4acC也检测到水稻,玉米,小鼠和人类的基因组DNA的质谱。我们的研究结果揭示了4acC作为一个迄今为止未知的DNA修饰在高等真核生物。我们确定了该标记与其他表观遗传标记在基因表达调控中的潜在相互作用。在线版本包含补充材料,可通过10.1186/s13059-021-02578-7获得。
Direct analogs of chemically modified bases that carry important epigenetic information, such as 5-methylcytosine (m5C)/5-methyldeoxycytosine (5mC), 5-hydroxymethylcytosine (hm5C)/5-hydroxymethyldeoxycytosine (5hmC), and N6-methyladenosine (m6A)/N6-methyldeoxyadenosine (6mA), are detected in both RNA and DNA, respectively. The modified base N4-acetylcytosine (ac4C) is well studied in RNAs, but its presence and epigenetic roles in cellular DNA have not been explored. Here, we demonstrate the existence of N4-acetyldeoxycytosine (4acC) in genomic DNA of Arabidopsis with multiple detection methods. Genome-wide profiling of 4acC modification reveals that 4acC peaks are mostly distributed in euchromatin regions and present in nearly half of the expressed protein-coding genes in Arabidopsis. 4acC is mainly located around transcription start sites and positively correlates with gene expression levels. Imbalance of 5mC does not directly affect 4acC modification. We also characterize the associations of 4acC with 5mC and histone modifications that cooperatively regulate gene expression. Moreover, 4acC is also detected in genomic DNA of rice, maize, mouse, and human by mass spectrometry. Our findings reveal 4acC as a hitherto unknown DNA modification in higher eukaryotes. We identify potential interactions of this mark with other epigenetic marks in gene expression regulation. The online version contains supplementary material available at 10.1186/s13059-021-02578-7.
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