A Lin-9 complex is recruited by B-Myb to activate transcription of G2/M genes in undifferentiated embryonal carcinoma cells

Oncogene. 2009 Apr 16;28(15):1737-47. doi: 10.1038/onc.2009.22. Epub 2009 Mar 2.


It has recently been discovered that cell-cycle gene transcription is regulated by a core complex named LINC that switches from a transcriptionally repressive complex in G(0)-G(1) with the p130 or p107 pocket proteins and E2F4 to a transcriptionally active complex in S-G(2) containing B-Myb. We have studied the function of LINC in F9 embryonal carcinoma cells, which are distinguished by a rapid cell cycle resulting from an extremely short G(1) phase. We show that suppressing expression of the LINC component, Lin-9, in F9 cells causes arrest in mitosis, and we have used this system to screen for transcriptional targets. In these cells, B-Myb was found in complexes with Lin-9 and several other LINC constituents, however, the pocket proteins did not associate with LINC unless F9 cells were differentiated. Lin-9 and B-Myb were both required for transcription of G(2)/M genes such as Cyclin B1 and Survivin. Moreover, B-Myb was demonstrated to recruit Lin-9 to the Survivin promoter through multiple Myb-binding sites. The demonstration that a B-Myb/LINC complex is vital for progression through mitosis in cells lacking a G(1)/S checkpoint has implications for both undifferentiated embryonal cells and for cancers in which pocket protein function is compromised.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Cycle Proteins / physiology*
  • Cell Division / genetics*
  • Chromatin Immunoprecipitation
  • Cyclin B / genetics
  • Cyclin B1
  • E2F Transcription Factors / physiology
  • Embryonal Carcinoma Stem Cells / metabolism*
  • G2 Phase / genetics*
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Promoter Regions, Genetic
  • Repressor Proteins
  • Survivin
  • Trans-Activators / physiology*
  • Transcriptional Activation*
  • Tumor Suppressor Proteins / physiology*


  • Birc5 protein, mouse
  • Ccnb1 protein, mouse
  • Cell Cycle Proteins
  • Cyclin B
  • Cyclin B1
  • E2F Transcription Factors
  • Inhibitor of Apoptosis Proteins
  • LIN-9 protein, mouse
  • Microtubule-Associated Proteins
  • Mybl2 protein, mouse
  • Repressor Proteins
  • Survivin
  • Trans-Activators
  • Tumor Suppressor Proteins