DNA Double-Strand Break (DSB) repair is essential to safeguard genome integrity. Upon DSBs, the ATM PI3K kinase rapidly triggers the establishment of megabase-sized, γH2AX-decorated chromatin domains which further act as seeds for the formation of DNA Damage Response (DDR) foci 1 . How these foci are rapidly assembled in order to establish a “repair-prone” environment within the nucleus is yet unclear. Topologically Associating Domains (TADs) are a key feature of 3D genome organization that compartmentalize transcription and replication, but little is known about their contribution to DNA repair processes 2 , 3 . Here we found that TADs are functional units of the DDR, instrumental for the correct establishment of γH2AX/53BP1 chromatin domains in a manner that involves one-sided cohesin-mediated loop extrusion on both sides of the DSB. We propose a model whereby H2AX-containing nucleosomes are rapidly phosphorylated as they actively pass by DSB-anchored cohesin. Our work highlights the critical impact of chromosome conformation in the maintenance of genome integrity and provides the first example of a chromatin modification established by loop extrusion.

In data analysis, latent variables play a central role because they help provide powerful insights into a wide variety of phenomena, ranging from biological to human sciences. The latent tree model, a particular type of probabilistic graphical models, deserves attention. Its simple structure - a tree - allows simple and efficient inference, while its latent variables capture complex relationships. In the past decade, the latent tree model has been subject to significant theoretical and methodological developments. In this review, we propose a comprehensive study of this model. First we summarize key ideas underlying the model. Second we explain how it can be efficiently learned from data. Third we illustrate its use within three types of applications: latent structure discovery, multidimensional clustering, and probabilistic inference. Finally, we conclude and give promising directions for future researches in this field