Department Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Bielefeld Institute for Bioinformatics Infrastructure, Department of Technology, Bielefeld University, Bielefeld, Germany.
J Exp Med. 2022 Oct 3;219(10). doi: 10.1084/jem.20210663. Epub 2022 Aug 8.
Epigenetic modifications such as DNA methylation play an essential role in imprinting specific transcriptional patterns in cells. We performed genome-wide DNA methylation profiling of murine lymph node-derived ILCs, which led to the identification of differentially methylated regions (DMRs) and the definition of epigenetic marker regions in ILCs. Marker regions were located in genes with a described function for ILCs, such as Tbx21, Gata3, or Il23r, but also in genes that have not been related to ILC biology. Methylation levels of the marker regions and expression of the associated genes were strongly correlated, indicating their functional relevance. Comparison with T helper cell methylomes revealed clear lineage differences, despite partial similarities in the methylation of specific ILC marker regions. IL-33-mediated challenge affected methylation of ILC2 epigenetic marker regions in the liver, while remaining relatively stable in the lung. In our study, we identified a set of epigenetic markers that can serve as a tool to study phenotypic and functional properties of ILCs.
表观遗传修饰，如 DNA 甲基化，在细胞中特异性转录模式的印迹中起着至关重要的作用。我们对来源于鼠淋巴结的 ILC 进行了全基因组 DNA 甲基化分析，这导致了差异甲基化区域 (DMRs) 的鉴定和 ILC 中表观遗传标记区域的定义。标记区域位于具有描述性 ILC 功能的基因中，如 Tbx21、Gata3 或 Il23r，但也位于尚未与 ILC 生物学相关的基因中。标记区域的甲基化水平与相关基因的表达强烈相关，表明它们具有功能相关性。与 Th 细胞甲基组的比较显示出明显的谱系差异，尽管特定 ILC 标记区域的甲基化存在部分相似性。IL-33 介导的挑战影响了肝脏中 ILC2 表观遗传标记区域的甲基化，而在肺部仍然相对稳定。在我们的研究中，我们确定了一组表观遗传标记，可作为研究 ILC 表型和功能特性的工具。
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