Chromosome structure
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We are interesting in studying how chromosomes are organized and the molecular factors responsible for this organization. Our model systems are chromosome organization in bacteria (B. subtilis and E. coli) and in eukaryotes (Drosophila Melanogaster). We investigate these processes by developing and applying super-resolution, advanced microscopy and chromosome capture conformation methods.
Our most salient recent research focuses on the study of We used microscopy methods to understand how DNA is organized in Drosophila cells Cattoni, Cardozo-Gizzi, Georgieva, etal., Single-cell absolute contact probability detection reveals chromosomes are organized by multiple low-frequency yet specific interactions, Nat. Comm 2017 At the kilo- to megabase pair scales, eukaryotic genomes are partitioned into self-interacting modules or topologically associated domains (TADs) that associate to form nuclear compartments. Here, we combine high-content super-resolution microscopies with state-of-the-art DNA-labeling methods to reveal the variability in the multiscale organization of the Drosophila genome. We find that association frequencies within TADs and between TAD borders are below ~10%, independently of TAD size, epigenetic state, or cell type. Critically, despite this large heterogeneity, we are able to visualize nanometer-sized epigenetic domains at the single-cell level. In addition, absolute contact frequencies within and between TADs are to a large extent defined by genomic distance, higher-order chromosome architecture, and epigenetic identity. We propose that TADs and compartments are organized by multiple, small-frequency, yet specific interactions that are regulated by epigenetics and transcriptional state. The architecture of the B. subtilis chromosome using super-resolution and 3C-methods (Marbouty et al. Condensin- and replication-mediated dynamic folding of a bacterial chromosome and its origin domain revealed by super-resolution imaging and Hi-C, Mol Cell 2015). The role of chromatin insulators in chromosome architecture in Drosophila (Vogelmann, et al. Chromatin insulator factors involved in long-range DNA interactions and their role in the folding of the Drosophila genome . PLoS Genetics 2014). We have also contributed recently a number of reviews on these topics, focusing on
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