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

• Published in: Nature communications Vol. 9; no. 1; pp. 1698 - 14
• Main Authors: Scharer, Christopher D., Barwick, Benjamin G., Guo, Muyao, Bally, Alexander P. R., Boss, Jeremy M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.04.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 38/39; 45/15; 45/91; 631/250/2502/2170; 631/337/100; 64/60; Accessibility; Animals; Cell differentiation; Cell Differentiation - genetics; Cell division; Cell Division - genetics; Cell Line, Tumor; Chromatin; Differentiation (biology); DNA Methylation - genetics; Enhancer of Zeste Homolog 2 Protein - antagonists & inhibitors; Enhancer of Zeste Homolog 2 Protein - genetics; Enhancer of Zeste Homolog 2 Protein - metabolism; Epigenesis, Genetic - genetics; Epigenetics; Gene expression; Gene regulation; Genes; Histones - metabolism; Humanities and Social Sciences; Immune response (humoral); Immunity, Humoral - genetics; Kinases; Lymphocytes B; Lymphocytes T; Metabolism; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Plasma; Plasma cells; Plasma Cells - physiology; Positive Regulatory Domain I-Binding Factor 1 - genetics; Positive Regulatory Domain I-Binding Factor 1 - metabolism; Primary Cell Culture; Promoter Regions, Genetic - genetics; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04125-8

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. During B cell differentiation, the role of different genomic loci in transcriptional and epigenetic regulation in vivo is not well defined. Here the authors use an in vivo B cell differentiation model to map cellular division-dependent cis -regulatory element road map with ATAC-seq.