BCL6-centric reorganization of the genome during B cell affinity maturation

ABSTRACT: During the humoral immune response mature B-cells undergo a dramatic change in phenotype to enable antibody affinity maturation in germinal centers (GCs). Here, we observe for the first time that these phenotypic changes are accompanied by large-scale reorganization of the genomic architecture that encodes the GCB-cell transcriptional program. The coordinate expression of genes that specify the GCB-cell phenotype – most prominently, BCL6 – is achieved through a non-random, multilayered, chromatin reorganization process involving i) increased promoter connectivity, ii) formation of higher-order enhancer networks, iii) 5’ to 3’ gene looping, and iv) merging of gene neighborhoods that share active epigenetic marks. These cell-specific events are closely linked to binding of GC transcription factors and the structural proteins CTCF and cohesin. The gene encoding the GC master regulator, BCL6, is an anchor point for the formation of GC-specific gene and enhancer loops on chromosome 3. Furthermore, through CRISPR-mediated knockout we demonstrate that a putative locus control region upstream of Bcl6 is required for GCB-cell formation in mice. Thus, architectural reorganization of phenotype-driving gene sets, including assembly of cell type-specific promoter and enhancer networks, may be key to controlling tissue-specific gene expression programs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE84022 | GEO | 2016/09/26

SECONDARY ACCESSION(S): PRJNA327832

REPOSITORIES: GEO