DNA甲基化
表观遗传学
生物
先天性淋巴细胞
表观遗传学
染色质
先天免疫系统
组蛋白
DNA去甲基化
体育锻炼的表观遗传学
转录因子
CpG站点
甲基化
差异甲基化区
细胞生物学
遗传学
DNA
基因
基因表达
免疫系统
作者
Vincent Peng,Xiaoyun Xing,Jennifer K. Bando,Tihana Tršan,Blanda Di Luccia,Patrick L. Collins,Daofeng Li,Wei-Le Wang,Hyung Joo Lee,Eugene M. Oltz,Ting Wang,Marco Colonna
标识
DOI:10.1038/s41590-022-01164-8
摘要
Innate lymphocytes encompass a diverse array of phenotypic identities with specialized functions. DNA methylation and hydroxymethylation are essential for epigenetic fidelity and fate commitment. The landscapes of these modifications are unknown in innate lymphocytes. Here, we characterized the whole-genome distribution of methyl-CpG and 5-hydroxymethylcytosine (5hmC) in mouse innate lymphoid cell 3 (ILC3), ILC2 and natural killer (NK) cells. We identified differentially methylated regions (DMRs) and differentially hydroxymethylated regions (DHMRs) between ILC and NK cell subsets and correlated them with transcriptional signatures. We associated lineage-determining transcription factors (LDTFs) with demethylation and demonstrated unique patterns of DNA methylation/hydroxymethylation in relationship to open chromatin regions (OCRs), histone modifications and TF-binding sites. We further identified an association between hydroxymethylation and NK cell superenhancers (SEs). Using mice lacking the DNA hydroxymethylase TET2, we showed the requirement for TET2 in optimal production of hallmark cytokines by ILC3s and interleukin-17A (IL-17A) by inflammatory ILC2s. These findings provide a powerful resource for studying innate lymphocyte epigenetic regulation and decode the regulatory logic governing their identity. Colonna and colleagues present a genome-wide characterization of DNA methylation and hydroxymethylation in innate lymphocytes and identify differentially methylated and hydroxymethylated regions between NK cells, ILC2s and ILC3s.
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