To better define the control of immune system regulation, we generated an atlas of microRNA (miRNA) expression from 63 mouse immune cell populations and connected these signatures with assay for transposase-accessible chromatin using sequencing (ATAC–seq), chromatin immunoprecipitation followed by sequencing (ChIP–seq) and nascent RNA profiles to establish a map of miRNA promoter and enhancer usage in immune cells. miRNA complexity was relatively low, with >90% of the miRNA compartment of each population comprising <75 miRNAs; however, each cell type had a unique miRNA signature. Integration of miRNA expression with chromatin accessibility revealed putative regulatory elements for differentially expressed miRNAs, including miR-21a, miR-146a and miR-223. The integrated maps suggest that many miRNAs utilize multiple promoters to reach high abundance and identified dominant and divergent miRNA regulatory elements between lineages and during development that may be used by clustered miRNAs, such as miR-99a/let-7c/miR-125b, to achieve distinct expression. These studies, with web-accessible data, help delineate the cis-regulatory elements controlling miRNA signatures of the immune system.

为了更好地定义免疫系统调节的控制，我们生成了 63 个小鼠免疫细胞群的 microRNA (miRNA) 表达图谱，并将这些特征与使用测序 (ATAC-seq)、染色质免疫沉淀和测序进行转座酶可及的染色质分析连接起来(ChIP–seq) 和新生 RNA 图谱，以建立免疫细胞中 miRNA 启动子和增强子使用图谱。 miRNA 复杂性相对较低，每个群体 >90% 的 miRNA 区室包含 <75 miRNA；然而，每种细胞类型都有独特的 miRNA 特征。 miRNA 表达与染色质可及性的整合揭示了差异表达 miRNA 的推定调控元件，包括 miR-21a、miR-146a 和 miR-223。整合图谱表明，许多 miRNA 利用多个启动子来达到高丰度，并鉴定了谱系之间和发育过程中的显性和差异性 miRNA 调控元件，这些元件可能被聚集的 miRNA（例如 miR-99a/let-7c/miR-125b）用来达到鲜明的表达效果。这些研究以及可通过网络获取的数据有助于描述控制免疫系统 miRNA 特征的顺式调控元件。