We study two emerging concepts in the field of chromatin structure that may govern cell fate: a) Nucleosome-positioning, which controls the accessibility of promoters as well as other genomic features. b) The assembly of higher-order chromatin structure called nuclear foci/bodies, which require DNA looping to mediate such long-range interactions, for example to activate a promoter from a far-located enhancer.
a) Very recent data showed that nucleosome positioning is under the influence of DNA-histone contacts. These interactions are however not stable and our recent work suggests that chromatin insulators like BEAF, which are able to block the spreading of heterochromatin towards active genes, may further regulate nucleosome positioning. Such type of regulation imply the binding of BEAF and its co-factors to elements we called ‘Nucleosome Associated Cis-Regulatory Elements’ (NACRE), which may contribute to the fine-tuning of the structural and functional organization of the genome into chromatin. Our unpublished work also suggests that the regulation of nucleosome positioning further involves numerous co-factors as well as epigenetic mechanisms.
b) BEAF insulators may further regulate the DREF-mediated activation of hundreds of genes that regulate cell proliferation (e.g. E2F, cdks). Such regulations involve long-range interactions between distinct BEAF binding sites, allowing the juxtaposed genes to be clustered into foci/bodies (see above scheme). We are currently studying how the binding of BEAF and its co-factors regulate DREF-mediated cell proliferation through the dynamic assembly of these bodies. Our research will provide a better understanding of the fundamental mechanisms that regulate the fine-tuning of cell proliferation by chromatin structure, through nucleosome positioning and the organization of chromatin into foci/bodies.