STRUCTURAL STUDIES OF EPIGENETIC REGULATORS

Brookhaven Science Assoc-Brookhaven Lab, Upton NY

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In the cell, repressed chromatin domains are thought to be regulated by factors that bind specifically to these loci. One such protein, HP1, is associated with pericentric heterochromatin and telomeres in Drosophila. An example of a complex is the Polycomb group complex, PRC1. Polycomb proteins are involved in the maintenance of repression of target genes during development.The structures of epigenetic regulators in complex with nucleosome arrays will provide us with mechanistic insights into chromatin condensation. These data should give novel insights into transcription repression mechanisms, the specific features of the chromatin structures that contribute to this repression and the evolution of repressive machineries. The results will help interpretation of genetic and biochemical data available on the PRC1 and HP1 systems, and will enable the design of new functional experiments. Given the important roles of these proteins in regulating cell growth and differentiation, and in cancer development, structural data of PRC1 and HP1 will be beneficial also for this area of research. An understanding of the mechanisms by which the PcG proteins and HP1 perform their role will be central to the development of novel therapies based on epigenetic gene silencing.