We seek to understand how packaging of the genome influences the information transmitted across generations. The cells that carry this information (sperm, eggs, and their developmental precursors, collectively known as germ cells) face a unique set of challenges. First, they must use the genetic information encoded in their nuclei to control their own development. Second, they must package the nuclear genome for transmission through the delicate process of fertilization, and prepare it to initiate the first stages of embryogenesis. Finally, they must protect the heritable nuclear genome from mutagenesis. All three of these factors impact the biology and long-term evolution of the germ cells and of the genome itself, as well as the extent to which epigenetic information is transmitted across generations.
We are using two complementary strategies to attack this problem. First, we examine the evolution of regulatory information and genome packaging in male germ cells by evaluating differences in genome-wide regulatory states in spermatogenic cells across multiple species. Second, we use genetic manipulation and epigenetic engineering in the mouse model to determine the functional significance of specific regulatory states. As a natural extension of these studies, we are also exploring ways in which epigenetically-inherited information impacts the developmental and disease phenotypes of offspring. We are particularly interested in the role of the ‘poised’ or bivalent histone modification state, characterized by the simultaneous presence of the activating histone modification H3K4me3 and the repressive histone modification H3K27me3.
See the Research Areas page for more information on individual projects.
Bluma Lesch's Yale faculty profile.