Histone modifications and their impact on the functions of the cohesin complex

• Applicant: Professorin Dr. Sandra Brigitte Hake
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 113520333

Post-translational modifications (PTMs) of histone proteins, the main constituents of chromatin, have crucial roles in the regulation of diverse cellular mechanisms. Histone PTMs function by either directly changing chromatin structure or by generating a binding-platform for effector proteins, which recognize the modification(s) and initiate events that lead to gene activation or silencing. In this study we plan to investigate the functional connection between histone H3 lysine 79 (H3K79) methylation and sister chromatid cohesion in vitro and in vivo. We have identified SMC1 and SMC3, two subunits of the cohesin complex, as binding proteins of unmodified H3K79 peptides. This interaction is sequence-specific and modification-dependent, because methylation of H3K79 and/or phosphorylation of the adjacent threonine 80 prevents SMC1 and SMC3 binding. Since the important question of how cohesin recognizes specific chromatin regions has remained open so far, our study will hopefully shed light on how SMC1 and SMC3 proteins interact with chromatin and what biological consequences such an association has for the cell.

• DFG Programme: Research Grants