Investigating Mechanisms by which Tandem Repeats Mediate b1 Paramutation

University Of Arizona, Tucson AZ

Investigators

Abstract

The control of where and when genes are expressed is fundamental to the development and function of all organisms. Genes are within DNA molecules that are packaged into chromosomes. How the genes are packaged, referred to as chromatin organization, and the activities of protein complexes that modulate chromatin organization, such as chromatin remodelling complexes, are crucial for correct gene regulation. Inappropriate activation or inactivation of genes affects growth, development and physiology, which impacts clinical medicine and agriculture. This project's experiments investigate chromatin-level gene interactions in maize (corn). Maize is an excellent model system, in that the genetic tools available allow experiments not possible in humans or most animals. Unlike certain model genetic systems such as yeast and fruit flies, maize has gene and chromosome organization similar to humans and other mammals. We study the regulated expression of the genes required for the synthesis of the purple anthocyanin pigments in maize. Changes in purple gene activity produce obvious visual changes in pigment, easily revealing gene activity and inactivity, providing a powerful system for experimentation. In particular this project studies paramutation, which occurs when two different forms of the same gene interact, and this interaction leads to a reduction in expression of one gene. This change in expression is passed on to progeny, resulting in altered gene expression in subsequent generations. With prior NSF funding this project completed a series of experiments that identified what regions of the gene are required for this phenomenon to occur and isolated a series of mutations in other genes that perturb this phenomenon. In addition, previous experiments demonstrated that paramutation is associated with specific chromatin changes that are transmitted to progeny. The experiments currently being pursued are designed to further characterize the DNA sequences required for paramutation and to test specific models for how distinct chromatin states are established, maintained and transmitted to progeny. As genetic mechanisms are frequently conserved between organisms, results from the experiments with maize will provide important paradigms for many species, such as mammals and other important plants, where genetic tools are not as well developed.