Spatial organization and nuclear positioning of murine immunoglobulin loci in developing B cells

Magdalena B Rother,Cornells Murre,Kevin Am Van Kester,Menno C Van Zelm,Jacgues Jm Van Dongen

doi:10.1186/1756-8935-6-s1-p71

Magdalena B Rother, Cornells Murre + Show 3 more

Open Access

https://doi.org/10.1186/1756-8935-6-s1-p71

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Abstract

Background Genomic DNA in eukaryotic cells is highly organized and shows multiple levels of compaction. Contraction and folding of DNA enables long-range interactions between widely dispersed genes to facilitate their expression. Furthermore, genes are positioned in the nucleus to either transcriptionally active or permissive compartments [1]. During B-cell development in the bone marrow, immunoglobulins (Ig) are assembled through stepwise recombination of V, (D) and J genes. Imaging studies have shown that Ig loci are organized into rosette-like clusters of loops and contract prior to rearrangement [2]. Moreover, during B cell development Ig loci change their nuclear positioning [3]. However, how the chromatin fiber is organized into higher-order structures and how this is regulated is still unknown.

Highlights

Genomic DNA in eukaryotic cells is highly organized and shows multiple levels of compaction
Spatial distant measurements between IGH and IGK probes showed that both loci were contracted in RAG1-/pro-B cells as compared with E2A-/- pre-pro-B cells
Our studies confirm that spatial chromatin organization of murine IGH and IGK changes during development

Summary

Background

Genomic DNA in eukaryotic cells is highly organized and shows multiple levels of compaction. Contraction and folding of DNA enables long-range interactions between widely dispersed genes to facilitate their expression. Genes are positioned in the nucleus to either transcriptionally active or permissive compartments [1]. During B-cell development in the bone marrow, immunoglobulins (Ig) are assembled through stepwise recombination of V, (D) and J genes. Imaging studies have shown that Ig loci are organized into rosette-like clusters of loops and contract prior to rearrangement [2]. During B cell development Ig loci change their nuclear positioning [3]. How the chromatin fiber is organized into higher-order structures and how this is regulated is still unknown

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Conclusions