N6-Methyldeoxyadenosine Marks Active Transcription Start Sites in Chlamydomonas

N6-methyldeoxyadenosine (6mA or m6A) is a DNA modification preserved in prokaryotes to eukaryotes. It is widespread in bacteria, and functions in DNA mismatch repair, chromosome segregation, and virulence regulation. In contrast, the distribution and function of 6mA in eukaryotes have been unclear. Here we present a comprehensive analysis of the 6mA landscape in the genome of Chlamydomonas using new sequencing approaches. We identified the 6mA modification in 84% of genes in Chlamydomonas. We found that 6mA mainly locates at ApT dinucleotides around transcription start sites (TSS) with a bimodal distribution, and appears to mark active genes. A periodic pattern of 6mA deposition was also observed at base resolution, which is associated with nucleosome distribution near the TSS, suggesting a possible role in nucleosome positioning. The new genome-wide mapping of 6mA and its unique distribution in the Chlamydomonas genome suggest potential regulatory roles of 6mA in gene expression in eukaryotic organisms.

N6-甲基脱氧腺苷（N6-methyldeoxyadenosine，简称6mA或m6A）是一类广泛存在于原核生物至真核生物中的DNA修饰。该修饰在细菌中分布广泛，参与DNA错配修复、染色体分离及毒力调控等重要生理过程。与之形成对比的是，真核生物中6mA的分布特征与生物学功能迄今仍未明确。本研究借助新型测序技术，对衣藻（Chlamydomonas）基因组的6mA分布图谱开展了全面解析。我们在衣藻84%的基因中检测到了6mA修饰，发现6mA主要富集于转录起始位点（transcription start sites, TSS）周边的ApT二核苷酸区域，呈现双峰分布特征，且可作为活跃基因的标记。此外，我们在碱基分辨率下观察到6mA沉积的周期性模式，该模式与转录起始位点附近的核小体分布高度相关，提示6mA可能在核小体定位过程中发挥潜在作用。本次全基因组水平的6mA定位分析及其在衣藻基因组中的独特分布特征，表明6mA在真核生物的基因表达调控中具备潜在的重要功能。