TY - JOUR
T1 - The Proteasome Restricts Permissive Transcription at Tissue-Specific Gene Loci in Embryonic Stem Cells
AU - Szutorisz, Henrietta
AU - Georgiou, Andrew
AU - Tora, László
AU - Dillon, Niall
N1 - Funding Information:
We thank Ana Pombo for critical comments on the manuscript, Francisco Ramirez for discussion on data analysis, M. Oulad-Abdelghani and the IGBMC antibody facility for monoclonal antibody generation, and C. Gaudon for advice on the α-Rpn12 antibody. This work was supported by the Medical Research Council UK and by a European Union Marie Curie RTN grant (HPRN-CT 00504228). H.S. was funded by an EU Marie Curie Intra-European Fellowship.
PY - 2006/12/29
Y1 - 2006/12/29
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33845645536&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2006.10.045
DO - 10.1016/j.cell.2006.10.045
M3 - Article
C2 - 17190601
AN - SCOPUS:33845645536
SN - 0092-8674
VL - 127
SP - 1375
EP - 1388
JO - Cell
JF - Cell
IS - 7
ER -