RESEARCH INTEREST

One of the most fascinating challenges in genome biology is deciphering the non-coding genomic landscape, as the majority of the eukaryotic complexity is thought to be encoded in our regulatory elements. Studies in our lab focus on the functional relationship between the regions that regulate DNA replication initiation (ORIs) and transcription initiation in mammalian cells. We are testing the hypothesis that ORIs are not randomly located across the chromosomes but actively positioned to coordinate DNA replication with other genomic functions, such as active transcription and chromatin organization. To test this hypothesis we combine genomic analysis by using microarrays with biochemical and molecular studies at specific promoter-ORIs using pluripotent, primary and differentiated mouse cells and human cell lines. Our specific approaches are:

1. Molecular analysis of DNA replication initiation at ORIs associated with active promoters. We have recently found that ORI activation is accompanied by the overproduction of short DNA fragments that have undergone several rounds of DNA synthesis during a single S-phase. These rereplicated DNA fragments derive from the nucleosome-free region surrounding the transcription initiation sites of active promoters associated with replication origins. These findings suggest a mechanistic link between the initiation of replication, transcription and chromatin organization whose interdependence we are currently investigating.