TY - JOUR
T1 - Evolutionarily Conserved Multisubunit RBL2/p130 and E2F4 Protein Complex Represses Human Cell Cycle-Dependent Genes in Quiescence
AU - Litovchick, Larisa
AU - Sadasivam, Subhashini
AU - Florens, Laurence
AU - Zhu, Xiaopeng
AU - Swanson, Selene K.
AU - Velmurugan, Soundarapandian
AU - Chen, Runsheng
AU - Washburn, Michael P.
AU - Liu, X. Shirley
AU - DeCaprio, James A.
N1 - Funding Information:
This work was funded in part by Public Health Service grants PO1 CA50661 and RO1 CA063113 (J.A.D.), HG004069-01 (X.S.L. and X.Z.), and Claudia Adams Barr Award for Cancer Research (L.L.). We thank N. Lents and B. Dynlacht for ChIP protocol and PCR primer sequences, S. Gaubatz for sharing unpublished results, and N. Dyson and C. Ceol for discussions. We acknowledge R. Toddings and K. Kashin for excellent technical assistance. V. Kashin provided initial computational analysis of the ChIP-chip data.
PY - 2007/5/25
Y1 - 2007/5/25
N2 - The mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence.
AB - The mammalian Retinoblastoma (RB) family including pRB, p107, and p130 represses E2F target genes through mechanisms that are not fully understood. In D. melanogaster, RB-dependent repression is mediated in part by the multisubunit protein complex Drosophila RBF, E2F, and Myb (dREAM) that contains homologs of the C. elegans synthetic multivulva class B (synMuvB) gene products. Using an integrated approach combining proteomics, genomics, and bioinformatic analyses, we identified a p130 complex termed DP, RB-like, E2F, and MuvB (DREAM) that contains mammalian homologs of synMuvB proteins LIN-9, LIN-37, LIN-52, LIN-54, and LIN-53/RBBP4. DREAM bound to more than 800 human promoters in G0 and was required for repression of E2F target genes. In S phase, MuvB proteins dissociated from p130 and formed a distinct submodule that bound MYB. This work reveals an evolutionarily conserved multisubunit protein complex that contains p130 and E2F4, but not pRB, and mediates the repression of cell cycle-dependent genes in quiescence.
KW - CELLCYCLE
KW - DNA
UR - http://www.scopus.com/inward/record.url?scp=34249109173&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249109173&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2007.04.015
DO - 10.1016/j.molcel.2007.04.015
M3 - Article
C2 - 17531812
AN - SCOPUS:34249109173
SN - 1097-2765
VL - 26
SP - 539
EP - 551
JO - Molecular Cell
JF - Molecular Cell
IS - 4
ER -