New roles for DNA XXXX modification, eRNA, anchors, and superanchors in developing B cell progenitors.

@entity7513 @entity406 @entity5538 @entity34650
B-cell fate is orchestrated by a series of well-characterized developmental regulators. Here, we found that the onset of B-cell development was accompanied by large-scale changes in DNA @entity5538 modifications associated with promoters, enhancers, and anchors. These changes were tightly linked to alterations in transcription factor occupancy and nascent RNA (eRNA) transcription. We found that the prepro-B to the pro-B-cell transition was associated with a global exchange of DNA @entity5538 modifications for polycomb-mediated repression at CpG islands. Hypomethylated regions were found exclusively in the active/permissive compartment of the nucleus and were predominantly associated with regulatory elements or anchors that orchestrate the folding patterns of the genome. We identified superanchors, characterized by clusters of hypomethylated @entity34650 ( @entity34650 )-bound elements, which were predominantly located at boundaries that define topological associated domains. A particularly prominent hypomethylated superanchor was positioned down-stream of the @entity7513 ( @entity7513 ) locus. Analysis of global @entity406 -cross-linking studies indicated that the @entity7513 locus superanchor interacts with the VH region repertoire across vast genomic distances. We propose that the @entity7513 locus superanchor sequesters the VH and DHJH regions into a spatial confined geometric environment to promote rapid first-passage times. Collectively, these studies demonstrate how, in developing B cells, DNA @entity5538 modifications associated with regulatory and architectural elements affect patterns of gene expression, folding patterns of the genome, and antigen receptor assembly.
