- CHROMATIN DOMAIN FORMATION, POSITION EFFECTS AND CHROMATIN BOUNDARIES
The chicken alpha- and beta-globin domains are two of the best-characterized developmentally regulated groups of genes. The organization of the genome into discrete structural and functional domains is increasingly recognized as one of the first steps in the regulation of gene expression. We would like to understand the contribution of boundary or insulator elements to domain formation and maintenance. In addition, we are interested in the capacity of insulator elements to protect a transgene against variability in expression, known as position effects, due to distinct integration sites in the genome. This property of insulator elements should be very useful in gene therapy protocols
- CHROMATIN STRUCTURE AND MECHANISMS OF ACTION OF REGULATORY ELEMENTS LOCATED AT THE 3 SIDE OF THE CHICKEN ALPHA-GLOBIN DOMAIN
For several years we have been working on the characterization of the silencer-enhancer elements located at the 3 side of the chicken alpha-globin domain. Several models had been proposed to describe their mechanisms of action. At the present time it remains unclear how these elements regulate gene expression during development. It is less clear if the domain and the chromatin structure of these elements can influence their regulatory functions.We are currently investigating the relationship between those long-distance regulatory elements and their chromatin structure. We predict that the chromatin structure of such elements plays a critical role in their developmentally regulated action
- EPIGENETIC REGULATION OF HUMAN TUMOR SUPPRESSOR GENE PROMOTERS
Abnormal epigenetic silencing of CpG-islands corresponding to tumor suppressor gene promoters appears to be a more frequent phenomenon in tumorigenesis than was previously anticipated. Evidence from our laboratory leads us to suggest a novel contribution of methylation-sensitive nuclear factors on tumor suppressor promoter regulation and protection against abnormal DNA methylation. More recently, we have been interested on member of Polycomb and Trithorax group of proteins and their influence over tumor suppressor gene regulation.