Within the nucleus, active gene loci tend to cluster together in the nuclear interior, while inactive genes are often found at the nuclear lamina. On , Vladimir Botchkarev, Michael Fessing and co-workers find that developmentally regulated gene expression from the epidermal differentiation complex (EDC) - a locus containing genes associated with epidermal barrier formation - is associated with changes in nuclear position. At early stages of mouse development, the EDC is silent and is located at the periphery, but it moves more centrally prior to gene activation and becomes associated with SC35 nuclear speckles - an indication of transcriptional activity. This relocation is dependent on the epidermal transcription factor p63. Moreover, the authors find that p63 directly regulates the expression of the chromatin remodeller Brg1, and that Brg1 is required for the relocation and activation of the EDC. These results underscore the importance of higher order chromatin structure for the regulation of gene expression, and identify a mechanism by which this nuclear organisation can be developmentally regulated.
