State Key Laboratory for Crop Genetics and Germplasm Enhancement, Bioinformatics Center, Academy for Advanced Interdisciplinary Studies, Nanjing Agricultural University, Nanjing, China.
Jiangbei New Area Biopharmaceutical Public Service Platform Co., Ltd., Nanjing, China.
Genome Biol. 2022 Jan 3;23(1):5. doi: 10.1186/s13059-021-02578-7.
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 N-methyladenosine (m6A)/N-methyldeoxyadenosine (6mA), are detected in both RNA and DNA, respectively. The modified base N-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 N-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.
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（m5C）/5-甲基脱氧胞嘧啶（5mC）、5-羟甲基胞嘧啶（hm5C）/5-羟甲基脱氧胞嘧啶（5hmC）和 N6-甲基腺嘌呤（m6A）/N6-甲基脱氧腺嘌呤（6mA），分别在 RNA 和 DNA 中被检测到。修饰碱基 N-乙酰胞嘧啶（ac4C）在 RNA 中得到了很好的研究，但它在细胞 DNA 中的存在和表观遗传作用尚未被探索。
在这里，我们通过多种检测方法证明了拟南芥基因组 DNA 中存在 N-乙酰脱氧胞嘧啶（4acC）。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，并且存在于拟南芥近一半的表达蛋白编码基因中。4acC 主要位于转录起始位点附近，与基因表达水平呈正相关。5mC 的失衡不会直接影响 4acC 的修饰。我们还描述了 4acC 与 5mC 和组蛋白修饰之间的关联，这些修饰共同调节基因表达。此外，通过质谱分析还在水稻、玉米、小鼠和人类的基因组 DNA 中检测到了 4acC。
我们的发现揭示了 4acC 是高等真核生物中一种迄今未知的 DNA 修饰。我们确定了该标记与基因表达调控中其他表观遗传标记的潜在相互作用。
