A novel strategy to identify proteins that interpret histone methylation patterns deposited by Set1 and Set2

• Applicant: Professor Dr. Sigurd Braun
• Subject Area: General Genetics and Functional Genome Biology
• Term: from 2006 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 31128325

Regulation of gene expression independent of the DMA sequence is referred to as epigenetic control; it affects the structure and accessibility of chromatin, particularly through histone modifications (e.g., acetylation, methylation). Inappropriate epigenetic regulation plays a key role in tumorigenesis. For example, the human leukemia protooncogenes MIL and NSD1 are mutated in different forms of leukemia, but how they contribute to tumorigenesis is not well understood. Both MLL and NSD1 encode histone methyltransferases, and their yeast orthologs, Set1 and Set2, methylate histone H3 at lysine residues 4 and 36, respectively. Recent data indicated that Set1 and Set2 function in preventing the spreading of silenced chromatin. The intention of this project is to gain new insights into the mechanisms by which Set1 and Set2 antagonize gene silencing. To this end, I will identify downstream effectors of Set1 and Set2, and study their role in anti-silencing. In particular, I will take a novel genome-wide approach using the DamiD technique to identify proteins that are recruited to histones in a manner that is dependent on Set1 or Set2 activity. Identified candidates will be further characterized in vivo by their contribution to prevent the spreading of heterochromatin and in vitro by biochemical binding studies.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Hiten Madhani