Puerto, MartaShukla, MamtaBujosa, PaulaPérez Roldán, JuanTorràs Llort, MònicaTamirisa, SrividyaCarbonell, AlbertSolé, CarmePuspo, Joynob AkterCummings, ChristopherNadal Clanchet, Eulàlia dePosas Garriga, FrancescAzorín Marín, FernandoRowley, M. Jordan2024-07-172024-07-172024Puerto M, Shukla M, Bujosa P, Pérez-Roldán J, Torràs-Llort M, Tamirisa S, et al. The zinc-finger protein Z4 cooperates with condensin II to regulate somatic chromosome pairing and 3D chromatin organization. Nucleic Acids Res. 2024 Jun 10;52(10):5596-609. DOI: 10.1093/nar/gkae1980305-1048http://hdl.handle.net/10230/60768Chromosome pairing constitutes an important level of genome organization, yet the mechanisms that regulate pairing in somatic cells and the impact on 3D chromatin organization are still poorly understood. Here, we address these questions in Drosophila, an organism with robust somatic pairing. In Drosophila, pairing preferentially occurs at loci consisting of numerous architectural protein binding sites (APBSs), suggesting a role of architectural proteins (APs) in pairing regulation. Amongst these, the anti-pairing function of the condensin II subunit CAP-H2 is well established. However, the factors that regulate CAP-H2 localization and action at APBSs remain largely unknown. Here, we identify two factors that control CAP-H2 occupancy at APBSs and, therefore, regulate pairing. We show that Z4, interacts with CAP-H2 and is required for its localization at APBSs. We also show that hyperosmotic cellular stress induces fast and reversible unpairing in a Z4/CAP-H2 dependent manner. Moreover, by combining the opposite effects of Z4 depletion and osmostress, we show that pairing correlates with the strength of intrachromosomal 3D interactions, such as active (A) compartment interactions, intragenic gene-loops, and polycomb (Pc)-mediated chromatin loops. Altogether, our results reveal new players in CAP-H2-mediated pairing regulation and the intimate interplay between inter-chromosomal and intra-chromosomal 3D interactions.application/pdfeng© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.comZincCromatinaCromosomesThe zinc-finger protein Z4 cooperates with condensin II to regulate somatic chromosome pairing and 3D chromatin organizationinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1093/nar/gkae198info:eu-repo/semantics/openAccess