The cis-regulatory atlas of the mouse immune system
Authors list
Hideyuki Yoshida Caleb A Lareau Ricardo N Ramirez Samuel A Rose Barbara Maier Aleksandra Wroblewska Fiona Desland Aleksey Chudnovskiy Arthur Mortha Claudia Dominguez Julie Tellier Edy Kim Dan Dwyer Susan Shinton Tsukasa Nabekura YiLin Qi Bingfei Yu Michelle Robinette Ki-Wook Kim Amy Wagers Andrew Rhoads Stephen L Nutt Brian D Brown Sara Mostafavi Jason D Buenrostro Christophe Benoist Immunological Genome Project
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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.
Journal details
Journal
Cell
Volume
176
Issue number
4
Pages
897-912.e20
Available online
Publication date
Full text links
Publisher website (DOI)
10.1016/j.cell.2018.12.036
Europe PubMed Central
30686579
Pubmed
30686579
Keywords
Type of publication
