Chromatin Structure and Function

The genetic information of eukaryotic cells is packaged in the form of chromatin. The fundamental unit of this packaging is the nucleosome, comprising two copies of each of four different histone proteins, around which is wrapped the double-stranded DNA. The nucleosome "beads" are packed together into higher orders of structure, so that the entire length of the eukaryotic chromosomes can fit into the confines of the cellular nucleus. This packaging creates a barrier for the molecular machinery that needs access to the information encoded in DNA for gene expression, replication, recombination, and chromosome stability. Thus, an important area of modern molecular biology focuses on the structure of chromatin and how the various machines gain access to the DNA sites at which they exert their function.

Research at MSU explores many features of chromatin structure and function. Covalent modifications to histone proteins, including acetylation, phosphorylation, and methylation, may affect the higher-order structure of chromatin and may also serve to recruit transcription or replication machinery to specific locations. Genetic studies of histone acetylation in yeast and in plants seeks to define the acetylation enzymes themselves, the proteins that recognize acetylated histones, and additional pathways that work in conjunction with acetylation in regulating chromatin function. Deacetylation of histones represents the other aspect of this control, and is frequently associated with gene silencing. Plant pathogens that secrete inhibitors of histone deacetylases are being studied to define the impact of that inhibition on both the host and the pathogen. The developmental impact of changes in chromatin at specific genes is being explored in mammalian white blood cells and in plants. The ways in which animal viruses employ or bypass chromatin in regulating viral gene expression are also being examined. The novel structure of telomeres, at the ends of chromosomes, and the mechanisms for maintaining that structure are crucial to chromosome stability, with profound implications for cancer and aging. As befits the wide-ranging biological impact of chromatin structure and function, many of these laboratories are also associated with other focus groups in transcriptional regulation, signal transduction, or cancer cell biology.