Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text (PDF, 699K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, R. Search for Related Content PubMed Articles by Williams, R. Social Bookmarking                            What's this?

Proteasomes on ES cell patrol

In ES cells (top), the proteasome (P) degrades transcription factors to prevent inappropriate transcription. DILLON/ELSEVIER

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 5 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 sites were mainly located around a known intergenic regulatory region. The many transcription factor binding sequences in such a region would be likely to attract and assemble nonspecific transcription factor complexes in the open chromatin environment of ES cells. Thus it appears that the proteasome's job is to ensure that these complexes don't inappropriately activate transcription.

Proteasome levels are similar in all cell types, yet in pre–B cells the transcription complex necessary for VpreB1 and 5 activation must be proteasome resistant. "There's some evidence that certain kinds of protein motifs get recognized by proteasomes," says Dillon. He suggests that these motifs might be available in ES cells but then get masked when the proteins form complexes that include tissue-specific transcription factors.

Although the exact mechanism is unknown, proteasome inhibition also up-regulated other tissue-specific loci in ES cells, suggesting that proteasome policing might be a general mechanism for keeping inappropriate transcription in check.

Reference:

Szutorisz, H., et al. 2006. Cell. 127:1375–1388.[CrossRef][Medline]

Ruth Williams

ruth.williams{at}rockefeller.edu

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF, 699K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, R. Search for Related Content PubMed Articles by Williams, R. Social Bookmarking                            What's this?