Stable unmethylated DNA demarcates expressed genes and their cis-regulatory space in plant genomes
Stable unmethylated DNA demarcates expressed genes and their cis-regulatory space in plant genomes
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DOI：
10.1073/pnas.2010250117
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发表时间：
2020-09-22
影响因子：
11.1
通讯作者：
Springer, Nathan M.
中科院分区：
文献类型：
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作者：
Crisp, Peter A.;Marand, Alexandre P.;Springer, Nathan M.
农作物的基因组序列继续以疯狂的速度产生。对这些基因组中的功能基因和调控元件进行完整注释仍然具有挑战性。染色质可及性测定能够发现功能元件；然而，要揭示顺式元件的完整组合，需要对细胞类型、组织、发育阶段和环境的许多组合进行分析。在这里，我们探索使用 DNA 甲基化图谱开发更完整注释的潜力。使用玉米的叶子组织，我们定义了大约 100,000 个非甲基化区域 (UMR)，占基因组的 5.8%；发现 33,375 个 UMR 的长度大于 2 kb。 UMR 在多种营养组织中高度稳定，并且它们捕获叶组织中绝大多数可接近的染色质区域。然而，许多 UMR 在叶子中是不可接近的，而这些代表了在特定细胞类型或发育阶段有可能变得可接近的区域。这些 UMR 通常出现在其他组织中表达的基因附近，并且富含转录因子的结合位点。叶子不可接近的 UMR 表现出独特的染色质修饰模式，并且因染色质与附近基因的相互作用而丰富。另外四个单子叶植物的总 UMR 空间范围为 80 至 120 兆碱基，考虑到基因组大小范围为 271 兆碱基至 4.8 吉碱基，这非常相似。总之，基于单个组织的概况，DNA 甲基化特征提供了强大的过滤器，可以将大型基因组提炼为假定的功能基因和调控元件的一小部分。
The genomic sequences of crops continue to be produced at a frenetic pace. It remains challenging to develop complete annotations of functional genes and regulatory elements in these genomes. Chromatin accessibility assays enable discovery of functional elements; however, to uncover the full portfolio of cis-elements would require profiling of many combinations of cell types, tissues, developmental stages, and environments. Here, we explore the potential to use DNA methylation profiles to develop more complete annotations. Using leaf tissue in maize, we define similar to 100,000 unmethylated regions (UMRs) that account for 5.8% of the genome; 33,375 UMRs are found greater than 2 kb from genes. UMRs are highly stable in multiple vegetative tissues, and they capture the vast majority of accessible chromatin regions from leaf tissue. However, many UMRs are not accessible in leaf, and these represent regions with potential to become accessible in specific cell types or developmental stages. These UMRs often occur near genes that are expressed in other tissues and are enriched for binding sites of transcription factors. The leaf-inaccessible UMRs exhibit unique chromatin modification patterns and are enriched for chromatin interactions with nearby genes. The total UMR space in four additional monocots ranges from 80 to 120 megabases, which is remarkably similar considering the range in genome size of 271 megabases to 4.8 gigabases. In summary, based on the profile from a single tissue, DNA methylation signatures provide powerful filters to distill large genomes down to the small fraction of putative functional genes and regulatory elements.