Multi-tiered Reorganization of the Genome during B Cell Affinity Maturation Anchored by a Germinal Center-Specific Locus Control Region Academic Article uri icon

Overview

MeSH Major

  • Antibody Affinity
  • B-Lymphocytes
  • Genome
  • Germinal Center
  • Locus Control Region

abstract

  • © 2016 Elsevier Inc.During the humoral immune response, B cells undergo a dramatic change in phenotype to enable antibody affinity maturation in germinal centers (GCs). Using genome-wide chromosomal conformation capture (Hi-C), we found that GC B cells undergo massive reorganization of the genomic architecture that encodes the GC B cell transcriptome. Coordinate expression of genes that specify the GC B cell phenotype—most prominently BCL6—was achieved through a multilayered chromatin reorganization process involving (1) increased promoter connectivity, (2) formation of enhancer networks, (3) 5′ to 3′ gene looping, and (4) merging of gene neighborhoods that share active epigenetic marks. BCL6 was an anchor point for the formation of GC-specific gene and enhancer loops on chromosome 3. Deletion of a GC-specific, highly interactive locus control region upstream of Bcl6 abrogated GC formation in mice. Thus, large-scale and multi-tiered genomic three-dimensional reorganization is required for coordinate expression of phenotype-driving gene sets that determine the unique characteristics of GC B cells.

publication date

  • September 20, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5033726

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2016.08.012

PubMed ID

  • 27637145

Additional Document Info

start page

  • 497

end page

  • 512

volume

  • 45

number

  • 3