Chromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions.

Diverse antibody repertoires are generated through remote genomic interactions involving immunoglobulin variable (V), diversity (D) and joining (J) gene segments. How such interactions are orchestrated remains unknown. Here we develop a strategy to track V-DJ motion in B-lymphocytes.

3D trajectories adopted by coding and regulatory DNA elements: first-passage times for genomic interactions.

During B lymphocyte development, immunoglobulin heavy-chain variable (VH), diversity (DH), and joining (JH) segments assemble to generate a diverse antigen receptor repertoire. Here, we have marked the distal VH and DH-JH-Eμ regions with Tet-operator binding sites and traced their 3D trajectories in pro-B cells transduced with a retrovirus encoding Tet-repressor-EGFP. We found that these elements displayed fractional Langevin motion (fLm) due to the viscoelastic hindrance from the surrounding network of proteins and chromatin fibers.

Positive intergenic feedback circuitry, involving EBF1 and FOXO1, orchestrates B-cell fate.

Recent studies have identified a number of transcriptional regulators, including E2A, early B-cell factor 1 (EBF1), FOXO1, and paired box gene 5 (PAX5), that promote early B-cell development. However, how this ensemble of regulators mechanistically promotes B-cell fate remains poorly understood. Here we demonstrate that B-cell development in FOXO1-deficient mice is arrested in the common lymphoid progenitor (CLP) LY6D(+) cell stage.

Transcription and recombination factories: common features?

There is now substantial evidence that the eukaryotic nucleus consists of highly organized structures. Among such structures are transcription factories that consist of an ensemble of genes recruited by the RNA polymerase machinery. Here we suggest that antigen receptor variable regions are similarly organized.

The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation.

Many steps in gene expression and mRNA biosynthesis are coupled to transcription elongation and organized through the C-terminal domain (CTD) of the large subunit of RNA polymerase II (RNAPII). We showed recently that Spt6, a transcription elongation factor and histone H3 chaperone, binds to the Ser2P CTD and recruits Iws1 and the REF1/Aly mRNA export adaptor to facilitate mRNA export. Here we show that Iws1 also recruits the HYPB/Setd2 histone methyltransferase to the RNAPII elongation complex and is required for H3K36 trimethylation (H3K36me3) across the transcribed region of the c-Myc, HIV-1, and PABPC1 genes in vivo.