|Institute of Molecular Biology,Genetics and Biotechnology|
|Foundation for Biomedical Research of the Academy of Athens
|Columbia University Medical School
|Biochemistry and Molecular Biophysics|
|Eukaryotic genes are organized inside nuclei in a chromatin-dependent manner. The role of chromatin in the control of gene expression has mainly been studied in yeast and in human cell lines, where it has been shown not only to be an organizer of the genome, but also a direct modifier of gene expression. In many cases gene activation cannot occur due to inhibitory local chromatin structure, such as the position of specific nucleosomes or presence of histone modifications.
Recent studies have shown that chromatin architecture can change and be propagated epigenetically in a cell-type and/or gene specific manner. However, due to the current experimental limitations on studying chromatin structure, it is not clear how widespread these mechanisms are, and whether they are used to control gene expression during animal development.
The fruit fly Drosophila melanogaster has been established as a model system for studying animal development. The characterization of developmentally regulated genes has provided many important insights into our understanding of development. In this proposal, I propose experiments that analyze the role that chromatin architecture plays during gene regulation in animal development, focusing on the regulation of Distalless (Dll), a gene required for leg development in Drosophila.
|Agelopoulos M and Thanos D
Epigenetic determination of a cell-specific gene expression program by ATF-2 and the histone variant macroH2A.
EMBO J. 2006 Oct 18;25(20):4843-53. Epub 2006 Oct 12