A biologist looks at the effect of a dynamic nuclear environment on gene expression.

In many organisms, including animals, genes are arranged linearly on chromosomes. But this linear order is largely meaningless during transcription, when RNA is made from DNA. Instead, a very different three-dimensional arrangement of genomic regions emerges in which structural flexibility and ability to reorganize become crucial to gene expression. Some regions loop out dynamically, moving far from their neighbours. Genes can participate in 'transcription hotspots' in close association with genes from other chromosomes. But the question remains as to what leads this dance. Is the chromosomal reorganization a cause or a consequence of transcription?

Using Hox clusters — groups of genes important in development — Wendy Bickmore of the Medical Research Council in Cambridge and her colleagues start to answer this question. Hoxb and Hoxd have very different environments in terms of their location on the chromosome and expression of their neighboring genes. The authors found that during tissue differentiation, Hox genes loop out and undergo active transcription. This reorganization then spreads from the Hox locus into adjacent genomic regions, but does not necessarily affect transcription of neighbouring genes (C. Morey Genome Res. doi:10.1101/gr.089045.108; 2009).

The authors propose that on activation, structural changes alter the constraints on genes' expression, allowing them to loop out and explore a much larger transcriptional environment within the nucleus. The team concludes that positioning outside of a chromosomal region is important for, but not a driver of, transcriptional activation.

These findings have broad implications: first, dynamic reorganization of chromosome territories is necessary but not sufficient for activation. Second, this reorganization is associated with modification to DNA's structural packaging, which can permanently alter a cell's nature.

Discuss this paper at http://blogs.nature.com/nature/journalclub