Our group has pioneered research in chromosomal architecture during B cell development, mainly focused on the role of cohesin during the development of B cell lymphoma. In this respect, we have shown that haploinsufficiency of the cohesin subunit Smc3 causes a decrease in intra-topologically-associating domain (TAD) interactions, which perturb enhancer-promoter contacts that sustain the expression of tumor suppressor genes.

Besides Smc3, other cohesin subunits and CTCF –cohesin's partner in crime in folding the genome– seem to have an essential role during these processes, making this an active research area in our lab.

Chromosomal architecture's role in controlling gene expression has long been proposed. And given the known function of cohesin and CTCF in folding the genome, they have been suggested to be critical for the transcriptional activation of genes. Yet, research using rapid degradation of cohesin and CTCF in ES cells failed to prove an extensive involvement of these factors in the maintenance of gene expression. Our lab has the mission to understand the precise participation of cohesin and CTCF during the establishment and maintenance of gene expression patterns under conditions in which cells undergo dynamic transitions that require extensive rewiring, like the ones that happen in germinal centers during the humoral immune response.

We have previously shown that cohesin cooperates with the IµBCL6 fusion oncogene to induce lymphoma. However, we have seen that cohesin and CTCF do not cooperate with any oncogene. Understanding the mechanisms by which chromosomal architecture cooperates with specific oncogenes will allow identifying potential novel targets for B cell lymphoma treatment.