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题名:The Proteasome Restricts Permissive Transcription at Tissue-Specific Gene Loci in Embryonic Stem Cells
作者:Henrietta Szutorisz, Andrew Georgiou,...
来源:Cell, Volume 127, Issue 7, 29 December 2006, Pages 1375-1388
URL :http://dx.doi.org/10.1016/j.cell.2006.10.045
日期:070115
摘要:Henrietta Szutorisz1, 3, , , Andrew Georgiou1, László Tora2 and Niall Dillon1, ,

1Gene Regulation and Chromatin Group, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, Du Cane Road, London W12 ONN, UK
2Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM, ULP, 1 rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, France

Received 13 April 2006; revised 28 August 2006; accepted 13 October 2006. Published: December 28, 2006. Available online 28 December 2006.


Summary

The ability of stem cells to activate different gene expression programs requires the choreographed assembly of trans-acting factors at enhancers and promoters during cell differentiation. In this study, we show that the proteasome acts on specific regulatory regions in embryonic stem (ES) cells to prevent incorrect transcriptional initiation. Chemical or siRNA-mediated inhibition of proteasome activity results in increased transcription factor and RNA polymerase II binding and leads to activation of cryptic promoters. Analysis of the binding profiles of different proteasome subunits in normal ES cells and following RNAi knockdown of individual subunits provides evidence for a targeted assembly of the 26S proteasome at specific regulatory elements. Our results suggest that the proteasome promotes a dynamic turnover of transcription factor and Pol II binding at tissue-specific gene domains in ES cells, thereby restricting permissive transcriptional activity and keeping the genes in a potentiated state, ready for activation at later stages.

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