Native E2F/RBF complexes contain Myb-interacting proteins and repress transcription of developmentally controlled E2F target genes.
The retinoblastoma tumor suppressor protein (pRb) regulates gene transcription by binding E2F transcription factors. pRb can recruit several repressor complexes to E2F bound promoters; however, native pRb repressor complexes have not been isolated. We have purified E2F/RBF repressor complexes from Drosophila embryo extracts and characterized their roles in E2F regulation. These complexes contain RBF, E2F, and Myb-interacting proteins that have previously been shown to control developmentally regulated patterns of DNA replication in follicle cells. The complexes localize to transcriptionally silent sites on polytene chromosomes and mediate stable repression of a specific set of E2F targets that have sex- and differentiation-specific expression patterns. Strikingly, seven of eight complex subunits are structurally and functionally related to C. elegans synMuv class B genes, which cooperate to control vulval differentiation in the worm. These results reveal an extensive evolutionary conservation of specific pRb repressor complexes that physically combine subunits with established roles in the regulation of transcription, DNA replication, and chromatin structure.
Lehrstuhl für Molekularbiologie, Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität, München, Germany.
Michael
M
Korenjak
Barbie
B
Taylor-Harding
Ulrich K
UK
Binné
John S
JS
Satterlee
Olivier
O
Stevaux
Rein
R
Aasland
Helen
H
White-Cooper
Nick
N
Dyson
Alexander
A
Brehm
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics; D050684:E2F Transcription Factors; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D020626:Oncogene Proteins v-myb / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D050684:E2F Transcription Factors; D006657:Histones; D046911:Macromolecular Substances; C489655:Mip130 protein, Drosophila; D020626:Oncogene Proteins v-myb; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C493765:efl-1 protein, C elegans