The function of dSU(VAR)3-9 in heterochromatin spreading and establishment

• Applicant: Professor Dr. Axel Imhof
• Subject Area: Developmental Biology
• Term: from 2002 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5368865

The molecular basis of several epigenetic phenomena is thought to depend on the chromatin structure of the studied gene. One of the most intriguing observations in this regard is the position effect in which a certain-mostly repressive-chromatin structure can dramatically affect the expression of neighbouring genes. While this effect has been intensively studied over the last decades, its molecular basis remains unclear. In the last two years it has become clear that modifications of histones play an important role in the establishment and maintenance of certain chromatin structures. It is therefore a very likely hypothesis that histone modifications are also involved in the process mentioned above. In this study we plan to address directly the question whether a particular histone modification, namely histone methylation, is involved in the apparent "spreading" effect and whether we can observe a physically spreading of methylation and chromatin associated proteins along the chromosome. To do this we will perform chromatin immunoprecipitation experiment with chromatin prepared from various mutant flies and tissue culture cells using antibodies against known heterochromatin associated proteins and modified histones. In a parallel approach we will attempt to reconstruct some of the aspects of heterochromatin in the test tube. We will then monitor spreading effects in order to define the minimal requirements for heterochromatin spreading in vitro.

• DFG Programme: Research Grants