Proteasomes on ES cell patrol

ES cell chromatin is more active and open than that of differentiated cells, yet tissue-specific genes are somehow kept quiet. A report by Henrietta Szutorisz, Niall Dillon (MRC Clinical Sciences Centre, London, UK), and colleagues suggests that proteasomes police such tissue-specific loci, degrading incoming transcription factors before they can initiate transcription.

The tissue-specific genes VpreB1 and λ5 share the same locus and are both strongly activated in pre–B cells but repressed in ES cells. The group now finds that repression in ES cells requires proteasome activity. Proteasome inhibition in ES cells led to increased transcription and the recruitment of a number of general transcription factors to the locus.

This transcriptional up-regulation, however, occurred all over the locus rather than at the genes' normal transcription start sites. The novel transcription start...