美国国家衰老研究所Ranjan Sen研究组发现，转录因子的不同组合决定人类免疫细胞的表观遗传特性。2021年10月26日，《免疫》杂志在线发表了这项成果。

研究人员确定了人类外周血中六种免疫细胞类型的谱系特异性DNA甲基化特征，并确定了它们与其他表观遗传学和转录组模式的关系。在每种细胞类型中，系谱特异性低甲基化的部位与转录因子的不同组合有关。相比之下，系谱特异性低甲基化的部位主要局限于适应性免疫细胞。PU.1的结合位点与不同类型细胞中的谱系特异性低甲基化和高甲基化有关，这表明它以一种依赖性的方式调节DNA甲基化。

这些观察表明，先天性和适应性免疫谱系是通过组合和情景依赖性使用关键转录因子的不同表观遗传机制来实现的。这种细胞特异性表观遗传学和转录模式是未来研究疾病和衰老中免疫失调的基础。

据介绍，表观遗传学的重编程是免疫细胞谱系特化的基础，但独特定义免疫细胞类型的模式和它们建立的机制仍不清楚。

附：英文原文

Title: DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity

Author: Roshni Roy, Senthilkumar Ramamoorthy, Benjamin D. Shapiro, Mary Kaileh, Dena Hernandez, Dimitra Sarantopoulou, Sampath Arepalli, Sren Boller, Amit Singh, Arsun Bektas, Jaekwan Kim, Ann Zenobia Moore, Toshiko Tanaka, Julia McKelvey, Linda Zukley, Cuong Nguyen, Tonya Wallace, Christopher Dunn, Robert Wersto, William Wood, Yulan Piao, Kevin G. Becker, Christopher Coletta, Supriyo De, Jyoti Misra Sen, Alexis Battle, Nan-ping Weng, Rudolf Grosschedl, Luigi Ferrucci, Ranjan Sen

Issue&Volume: 2021-10-26

Abstract: Epigenetic reprogramming underlies specification of immune cell lineages, but patternsthat uniquely define immune cell types and the mechanisms by which they are establishedremain unclear. Here, we identified lineage-specific DNA methylation signatures ofsix immune cell types from human peripheral blood and determined their relationshipto other epigenetic and transcriptomic patterns. Sites of lineage-specific hypomethylationwere associated with distinct combinations of transcription factors in each cell type.By contrast, sites of lineage-specific hypermethylation were restricted mostly toadaptive immune cells. PU.1 binding sites were associated with lineage-specific hypo-and hypermethylation in different cell types, suggesting that it regulates DNA methylationin a context-dependent manner. These observations indicate that innate and adaptiveimmune lineages are specified by distinct epigenetic mechanisms via combinatorialand context-dependent use of key transcription factors. The cell-specific epigenomicsand transcriptional patterns identified serve as a foundation for future studies onimmune dysregulation in diseases and aging.

DOI: 10.1016/j.immuni.2021.10.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00407-6