Native E2F/RBF Complexes Contain Myb-interacting Proteins and Repress Transcription of Developmentally Controlled E2F Target Genes

Cell. 2004 Oct 15;119(2):181-93. doi: 10.1016/j.cell.2004.09.034.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / anatomy & histology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / isolation & purification
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA Replication
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / isolation & purification
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics
  • E2F Transcription Factors
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental*
  • Histones / chemistry
  • Histones / metabolism
  • Humans
  • Macromolecular Substances
  • Molecular Sequence Data
  • Oncogene Proteins v-myb / genetics
  • Oncogene Proteins v-myb / metabolism*
  • Protein Subunits / genetics
  • Protein Subunits / isolation & purification
  • Protein Subunits / metabolism
  • RNA Interference
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / isolation & purification
  • Retinoblastoma Protein / metabolism*
  • Sequence Alignment
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Chromatin
  • DNA-Binding Proteins
  • Drosophila Proteins
  • E2F Transcription Factors
  • Histones
  • Macromolecular Substances
  • Mip130 protein, Drosophila
  • Oncogene Proteins v-myb
  • Protein Subunits
  • Recombinant Fusion Proteins
  • Retinoblastoma Protein
  • Transcription Factors
  • efl-1 protein, C elegans