Plasma cell differentiation is controlled by multiple cell division-coupled epigenetic programs

• Type of Material: Article
• Authors: Christopher Scharer, Emory University; Benjamin G. Barwick, Emory University; Muyao Guo, Emory University; Alexander P.R. Bally, Emory University; Jeremy Boss, Emory University
• Language: English
• Date: 2018-04-27
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-018-04125-8
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 9
• Start Page: 1698
• End Page: 1698
• Grant/Funding Information: B.G.B. was supported by NIH T32 GM0008490 and F31 AI112261.; This work was supported by NIH grants P01 AI125180 and R01 AI123733 to J.M.B.
• Keywords: BLIMP-1; METHYLATION; Science & Technology - Other Topics; LYMPHOMAGENESIS; Multidisciplinary Sciences; Science & Technology; GERMINAL CENTER B; GENE-EXPRESSION; CHROMATIN; CIITA; REGULATORY ELEMENTS; EZH2; ACCESSIBILITY
• Research Categories: Health Sciences, Oncology; Biology, Microbiology; Health Sciences, Immunology

Abstract

The genomic loci associated with B cell differentiation that are subject to transcriptional and epigenetic regulation in vivo are not well defined, leaving a gap in our understanding of the development of humoral immune responses. Here, using an in vivo T cell independent B cell differentiation model, we define a cellular division-dependent cis-regulatory element road map using ATAC-seq. Chromatin accessibility changes correlate with gene expression and reveal the reprogramming of transcriptional networks and the genes they regulate at specific cell divisions. A subset of genes in naive B cells display accessible promoters in the absence of transcription and are marked by H3K27me3, an EZH2 catalyzed repressive modification. Such genes encode regulators of cell division and metabolism and include the essential plasma cell transcription factor Blimp-1. Chemical inhibition of EZH2 results in enhanced plasma cell formation, increased expression of the above gene set, and premature expression of Blimp-1 ex vivo. These data provide insights into cell-division coupled epigenetic and transcriptional processes that program plasma cells.