The role of novel human synMuv-like proteins in gene expression and cell cycle regulation

• Applicant: Professor Dr. Stefan Gaubatz
• Subject Area: Cell Biology
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 35305910

In the past funding period we have identified a novel human complex that has an essential role in G2 progression. This complex, called LINC, dynamically associates with pocket proteins, E2F and B-MYB in a cell cycle dependent manner: In quiescent cells, LINC binds to p130/E2F4 and in S-phase to B-MYB. LINC/B-MYB associates with the promoters of G2/M genes and mediates their cell cycle-dependent activation. In order to learn more about gene regulation by LINC, we characterized LIN-54, an evolutionary conserved subunit, in more detail. LIN-54 has a DNA-binding domain, and surprising-ly, we found that its binding to the cdc2 promoter depends on two distinct binding sites. Because two other subunits of LINC also exhibit sequence-specific DNA-binding, this suggests that activation of mitotic genes involves changes in the chromatin conformation through different modes of LINC binding in distinct phases of the cell cycle. To test this idea, we will analyze how the complex is targeted to mitotic promoters in different phases of the cell cycle. We will also test which steps of promoter activation are dependent on LINC. Secondly, we will investigate to what extend cell cycle progression depends on DNA-binding and transcriptional activation by LINC. Finally, we propose to develop tools to analyze the regulation of mitotic genes at the single-cell level.

• DFG Programme: Research Grants