Nuclear organisation of immunoglobulin recombination
The immunoglobulin heavy chain (Igh) and immunoglobulin kappa light chain (Igk) loci are the largest loci in the genome and must move in 3D nuclear space to juxtapose and recombine distal V , D and J genes.
They use a complex set of epigenetic mechanisms including histone modifications, DNA looping and non-coding RNA transcription, and are the ultimate paradigm of nuclear organization.
We are particularly interested in the roles of non-coding RNA transcription and nuclear dynamics in V(D)J recombination of the Ig loci. Over 90% of transcribed sequences in the genome are non-coding, ie do not produce protein. Further, 20% of RNAs come from the non-coding strand (antisense transcripts).
A key unanswered question in gene regulation is: what is function of non-coding transcription and the resulting transcripts? They have been proposed to regulate activation of large chromatin domains differentially expressed in different cell lineages, or bring distal promoters and enhancers together.