The control of DNA based processes in biology is crucial for an organism s life, development, reproduction and evolution. In fact, deregulation of gene expression, of the replication program, of DNA repair or recombination has often disastrous consequences. The eukaryotic genome is structurally and functionally organized into chromatin by a highly complex mixture of proteins that control access to the DNA. In particular, heterochromatin proteins play a prominent role in this control. Genetics, biochemistry and molecular biology identified many players involved in eukaryotic DNA biology and provided everything we currently know about it. However the full composition of a given locus remains largely obscure and just like any object under scientific study, knowing the composition is an absolute pre-requisite for a full understanding of its features. Consequently, the nature of the interactions between chromatin structural components and DNA machineries is poorly understood and the elaboration of models from rather incompletely characterized systems can be misleading. During my post-doctorate, I have developed an unbiased approach for the in vivo purification of chromatin proteins in a locus specific manner, and I intend to apply this new technology in combination with a genetic approach. Monitoring the consequence of heterochromatin protein loss on the full composition of regulated loci will allow a deeper understanding of the role these proteins in the regulation of eukaryotic genome biology.