The cis-Regulatory Atlas of the Mouse Immune System

Abstract

A complete chart of cis-regulatory elements and their dynamic activity is necessary to understand the transcriptional basis of differentiation and function of an organ system. We generated matched epigenome and transcriptome measurements in 86 primary cell-types that span the mouse immune system and its differentiation cascades. This breadth of data enables variance components analysis which suggests that genes fall into two distinct classes, controlled by either enhancer- or promoter-driven logic, and multiple regression that connects genes to the enhancers that regulate them. Relating transcription factor (TF) expression to the genome-wide accessibility of their binding motifs classifies them as predominantly openers or closers of local chromatin accessibility, pinpointing specific cis-regulatory elements where binding of given TFs is likely functionally relevant, validated by ChIP-seq. Overall, this cis-regulatory atlas provides a trove of information on transcriptional regulation through immune differentiation, and a foundational scaffold to define key regulatory events throughout the immunological genome. A cis-regulatory map of the mouse immune system illuminates gene expression patterns and regulatory logic across 86 primary cell types and pairs immune transcription factors with cell type-specific regulatory elements.