RESEARCH SUMMARY

The research in the Bartolomei laboratory uses the mouse as a model system to study the mechanisms that control genomic imprinting and X inactivation. Both phenomena employ genetic and epigenetic strategies to distinguish and stably inactivate parental alleles or chromosomes.

Genomic imprinting affects a small number of genes and results in the unequal expression of the maternal and paternal alleles of these genes. The majority of projects in the laboratory focus on a cluster of imprinted genes on the distal end of mouse chromosome 7, where the maternally expressed H19 and the paternally expressed Igf2 genes reside.

We are using gene targeting and transgenic experiments to identify critical factors and sequence involved in the imprinting of these two genes. We are also using various physiological and developmental perturbations such as embryo culture, DNA methyltransferase mutant mice and mouse cloning to investigate critical imprinting processes.

While genomic imprinting regulates the parental expression of specific genes throughout the genome, X inactivation results in the silencing of most genes on one of the two X chromosomes in females to achieve dosage compensation between males and females.

For the study of X inactivation we have employed chemical mutagenesis to identify factors involved in the choice of which chromosome is to be active/inactive and have isolated autosomal mutations with dominant effects on X inactivation patterns. These mutations are currently being characterized, mapped and identified.

Click here for a list of publications (searches the National Library of Medicine's PubMed database.)