A microRNA expression and regulatory element activity atlas of the mouse immune system

Abstract

microRNAs (miRNA) play an important role in immune system development and function, often participating in regulatory networks with the transcription factors that drive their expression. However, many of these relationships remain obscured because regulatory elements controlling miRNA expression in different immune cells remain largely uncharacterized. To address this, we analyzed miRNA expression and open chromatin regions (OCR) from >60 immune cell populations. This enabled us to establish maps of miRNA promoter and enhancer usage across the immune system. Unique miRNA signatures within different populations were associated with local chromatin accessibility changes, revealing putative regulatory elements for differentially expressed miRNAs. These maps suggest many miRNAs utilize multiple promoters to increase abundance, and also identified dominant and divergent miRNA regulatory elements between lineages and during immune cell development, as well as between closely clustered miRNAs. This study provides insight into the miRNA regulatory network of the immune system and is a resource for further discovery.