IL-7R signaling activates widespread V and D gene usage to drive antibody diversity in bone marrow B cells.

Generation of the primary antibody repertoire requires V(D)J recombination of hundreds of gene segments in the immunoglobulin heavy chain (Igh) locus. The role of interleukin-7 receptor (IL-7R) signaling in Igh recombination has been difficult to partition from its role in B cell survival and proliferation. With a detailed description of the Igh repertoire in murine IL-7Rα bone marrow B cells, we demonstrate that IL-7R signaling profoundly influences V gene selection during V-to-DJ recombination.

Two Mutually Exclusive Local Chromatin States Drive Efficient V(D)J Recombination.

Variable (V), diversity (D), and joining (J) (V(D)J) recombination is the first determinant of antigen receptor diversity. Understanding how recombination is regulated requires a comprehensive, unbiased readout of V gene usage. We have developed VDJ sequencing (VDJ-seq), a DNA-based next-generation-sequencing technique that quantitatively profiles recombination products.

NuRD-dependent DNA methylation prevents ES cells from accessing a trophectoderm fate.

Embryonic Stem (ES) cells are able to give rise to the three germ layers of the embryo but are prevented from contributing to the trophoblast. The molecular nature of this barrier between embryonic and trophectodermal cell fates is not clear, but is known to involve DNA methylation. Here we demonstrate that the Nucleosome Remodeling and Deacetylation (NuRD) co-repressor complex maintains the developmental barrier between embryonic and trophectodermal cell fates by maintaining transcriptional silencing of trophectoderm determinant genes in ES cells.