The intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing and microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles in interpreting experimental observations by reconstructing high-resolution structural ensembles and uncovering organization principles. However, the absence of standardized modeling tools poses challenges for furthering nuclear investigations. We present OpenNucleome—an open-source software designed for conducting GPU-accelerated molecular dynamics simulations of the human nucleus. OpenNucleome offers particle-based representations of chromosomes at a resolution of 100 KB, encompassing nuclear lamina, nucleoli, and speckles. This software furnishes highly accurate structural models of nuclear architecture, affording the means for dynamic simulations of condensate formation, fusion, and exploration of non-equilibrium effects. We applied OpenNucleome to uncover the mechanisms driving the emergence of ‘fixed points’ within the nucleus—signifying genomic loci robustly anchored in proximity to specific nuclear bodies for functional purposes. This anchoring remains resilient even amidst significant fluctuations in chromosome radial positions and nuclear shapes within individual cells. Our findings lend support to a nuclear zoning model that elucidates genome functionality. We anticipate OpenNucleome to serve as a valuable tool for nuclear investigations, streamlining mechanistic explorations and enhancing the interpretation of experimental observations.

Most teleost fishes exhibit a biphasic life history with a larval oceanic phase that is transformed into morphologically and physiologically different demersal, benthic, or pelagic juveniles. This process of transformation is characterized by a myriad of hormone-induced changes, during the often abrupt transition between larval and juvenile phases called metamorphosis. Thyroid hormones (TH) are known to be instrumental in triggering and coordinating this transformation but other hormonal systems such as corticoids, might be also involved as it is the case in amphibians. In order to investigate the potential involvement of these two hormonal pathways in marine fish post-embryonic development, we used the Malabar grouper (Epinephelus malabaricus) as a model system. We assembled a chromosome-scale genome sequence and conducted a transcriptomic analysis of nine larval developmental stages. We studied the expression patterns of genes involved in TH and corticoid pathways, as well as four biological processes known to be regulated by TH in other teleost species: ossification, pigmentation, visual perception, and metabolism. Surprisingly, we observed an activation of many of the same pathways involved in metamorphosis also at an early stage of the larval development, suggesting an additional implication of these pathways in the formation of early larval features. Overall, our data brings new evidence to the controversial interplay between corticoids and thyroid hormones during metamorphosis as well as, surprisingly, during the early larval development. Further experiments will be needed to investigate the precise role of both pathways during these two distinct periods and whether an early activation of both corticoid and TH pathways occurs in other teleost species.