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2016 ; 45
(3
): 497-512
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Multi-tiered Reorganization of the Genome during B Cell Affinity Maturation
Anchored by a Germinal Center-Specific Locus Control Region
#MMPMID27637145
Bunting KL
; Soong TD
; Singh R
; Jiang Y
; Béguelin W
; Poloway DW
; Swed BL
; Hatzi K
; Reisacher W
; Teater M
; Elemento O
; Melnick AM
Immunity
2016[Sep]; 45
(3
): 497-512
PMID27637145
show ga
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.
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