Biology subjects

Hovet, O.

Publications and source records attributed to Hovet, O..

3 recordsLinked to original sources

bioRxiv2026

HP1α depletion and TGFβ activation exert antagonistic effects on 3D genome organization

The three-dimensional (3D) organization of the human genome plays a critical role in regulating gene expression and is frequently disrupted in cancer. However, how key factors like Heterochromatin Protein 1 alpha (HP1) and Transforming Growth Factor beta (TGF{beta}) remodel this architecture to drive tumorigenesis remains poorly understood. We investigated the effects of HP1 knockdown and TGF{beta} treatment on higher-order chromatin structure and gene expression in human mammary epithelial cells. Our findings reveal that HP1 depletion and TGF{beta} stimulation exert distinct and opposing effects on genome compartmentalization and sub compartmentalization. HP1 knockdown drives a genome-wide shift of chromatin from transcriptionally inactive B compartments to active A compartments. This is accompanied by a stepwise redistribution of A subcompartments toward the most transcriptionally active state (A3), and the upregulation of oncogenic genes involved in EMT and proliferation. In contrast, TGF{beta} treatment promotes chromatin compaction, increases the proportion of B compartments, and drives a stepwise reduction in active A subcompartments. Our results highlight the differential roles of HP1 and TGF{beta} in shaping the 3D genome and underscore how precise, stepwise architectural changes contribute to malignant transformation. This study provides critical insight into how chromatin architecture acts as a regulatory layer in breast cancer development. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/705282v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@11c7475org.highwire.dtl.DTLVardef@121b305org.highwire.dtl.DTLVardef@1704b64org.highwire.dtl.DTLVardef@1659c34_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACT C_FIG

genomics↗

bioRxiv2025

The 3D nuclear position and compartmentalization of genes prime their response to mechano-confinement

Cells continuously receive mechanical inputs from their environment. For example, during migration in narrow spaces, or in solid tumors, cells and their nuclei experience confinement which they sense and respond to. Emerging evidence identifies the genome as a central mediator of these responses, dynamically reorganizing its three-dimensional (3D) structure to regulate both short- and long-term gene expression programs, enabling cellular adaptation to mechanical constraints. However, the mechanisms underlying such responses, especially those linking the 3D genome and transcriptome, are unknown. Here, we utilize controlled cell confinement followed by Hi-C and transcriptome analyses to map and model temporal responses to mechano-confinement in the 3D genome. We identify clusters of genes (termed "TECs") exhibiting coordinated temporal transcriptional responses tied to their differential radial positioning within the nucleus. Additionally, we uncover a genome-wide, partially reversible response, wherein chromosomes reposition under confinement to enhance select genome compartments, aligning with temporal gene regulation patterns. Specifically, one such cluster, TEC7, is linked to 3D genome restructuring and nuclear translocation of NF-{kappa}B, driving cytokine expression and secretion. Our findings reveal how 3D genome reorganization and transcriptional programs can drive mechanoresponses, opening up for new views into the mechanisms of mechanogenomic regulation in health and disease.

genomics↗

bioRxiv2022

The structural basis of the multi-step allosteric activation of Aurora B kinase

Aurora B, together with IN-box, the C-terminal part of INCENP, forms an enzymatic complex that ensures faithful cell division. The [Aurora B/IN-box] complex is activated by autophosphorylation in the Aurora B activation loop and in IN-box, but it is not clear how these phosphorylations activate the enzyme. We used a combination of experimental and computational studies to investigate the effects of phosphorylation on the molecular dynamics and structure of [Aurora B/IN-box]. In addition, we generated partially phosphorylated intermediates to analyze the contribution of each phosphorylation independently. We found that the dynamics of Aurora and IN-box are interconnected, and IN-box plays both positive and negative regulatory roles depending on the phosphorylation status of the enzyme complex. Phosphorylation in the activation loop of Aurora B occurs intramolecularly and prepares the enzyme complex for activation, but two phosphorylated sites are synergistically responsible for full enzyme activity.

biochemistry↗