The cis-Regulatory Atlas of the Mouse Immune System

Cell. 2019 Feb 7;176(4):897-912.e20. doi: 10.1016/j.cell.2018.12.036. Epub 2019 Jan 24.

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 enable variance components analysis that 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 chromatin immunoprecipitation sequencing (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.

Keywords: ATAC-seq; Transcriptional regulation; chromatin; enhancer; epigenomics; immune cell differentiation; transcription factor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Chromatin
  • Chromatin Immunoprecipitation / methods
  • Enhancer Elements, Genetic / genetics
  • Epigenomics / methods
  • Gene Expression Regulation / genetics
  • Immune System / immunology*
  • Immune System / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Promoter Regions, Genetic / genetics
  • Protein Binding / genetics
  • Regulatory Elements, Transcriptional / genetics*
  • Transcription Factors / metabolism
  • Transcriptome / genetics

Substances

  • Chromatin
  • Transcription Factors