LINC, a human complex that is related to pRB-containing complexes in invertebrates regulates the expression of G2/M genes

Cell Cycle. 2007 Aug 1;6(15):1903-13. doi: 10.4161/cc.6.15.4512. Epub 2007 May 25.

Abstract

Here we report the identification of the LIN complex (LINC), a human multiprotein complex that is required for transcriptional activation of G2/M genes. LINC is related to the recently identified dREAM and DRM complexes of Drosophila and C. elegans that contain homologs of the mammalian retinoblastoma tumor suppressor protein. The LINC core complex consists of at least five subunits including the chromatin-associated LIN-9 and RbAp48 proteins. LINC dynamically associates with pocket proteins, E2F and B-MYB during the cell cycle. In quiescent cells, LINC binds to p130 and E2F4. During cell cycle entry, E2F4 and p130 dissociate and LINC switches to B-MYB and p107. Chromatin Immunoprecipitation experiments demonstrate that LINC associates with a large number of E2F-regulated promoters in quiescent cells. However, RNAi experiments reveal that LINC is not required for repression. In S-phase, LINC selectively binds to the promoters of G2/M genes whose products are required for mitosis and plays an important role in their cell cycle dependent activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Cell Line
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • E2F Transcription Factors / genetics
  • E2F Transcription Factors / metabolism
  • G2 Phase / genetics*
  • Gene Expression Regulation / genetics*
  • Humans
  • Mitosis / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • RNA Interference
  • Retinoblastoma Protein / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / isolation & purification
  • Trans-Activators / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • E2F Transcription Factors
  • LIN9 protein, human
  • Lin-37 protein, human
  • Lin-54 protein, human
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Protein Subunits
  • Retinoblastoma Protein
  • Trans-Activators
  • Tumor Suppressor Proteins