Biology subjects

van Rijnberk, L. M.

Publications and source records attributed to van Rijnberk, L. M..

3 recordsLinked to original sources

bioRxiv2025

Transcriptional repression of central spindle factors controls endomitosis in the C. elegans intestine

During development, many cell types transition from canonical to non-canonical cell cycles, such as endomitosis and endoreplication, in which they duplicate their DNA but do not divide, giving rise to polyploidy. Little is known on the regulation of endomitosis, where cells enter M phase, but do not perform cytokinesis. Here, we investigate how cells initiate and execute endomitosis in the C. elegans intestine and find that endomitotic cells fail to assemble a central spindle or initiate cytokinetic furrowing. We find that endomitotic cells transcriptionally repress multiple cytokinesis regulators, especially the central spindle factors ZEN-4Mklp1, CYK-4RacGap1 and SPD-1Prc1. Intestinal cells lose the capacity to perform cytokinesis in late embryogenesis, and we find that the conserved DREAM (DP, RB-related, E2F and MuvB) complex is involved in the repression of central spindle genes. Together, our work demonstrates that the transition to endomitosis is a well-defined switch that relies on the transcriptional repression of cytokinesis genes.

developmental biology↗

bioRxiv2021

Endomitosis controls tissue-specific gene expression during development

Polyploid cells contain more than two copies of the genome and are found in many plant and animal tissues. Different types of polyploidy exist, in which the genome is confined to either one nucleus (mononucleation) or two or more nuclei (multinucleation). Despite the widespread occurrence of polyploidy, the functional significance of different types of polyploidy are largely unknown. Here, we assess the function of multinucleation in C. elegans intestinal cells through specific inhibition of binucleation without altering genome ploidy. Through single worm RNA sequencing, we find that binucleation is important for tissuespecific gene expression, most prominently for genes that show a rapid upregulation at the transition from larval development to adulthood. Regulated genes include vitellogenins, which encode yolk proteins that facilitate nutrient transport to the germline. We find that reduced expression of vitellogenins in mononucleated intestinal cells leads to progeny with developmental delays and reduced fitness. Together, our results show that binucleation facilitates rapid upregulation of intestine-specific gene expression during development, independently of genome ploidy, underscoring the importance of spatial genome organization for polyploid cell function.

cell biology↗

bioRxiv2020

Excessive E2F transcription in single cancer cells precludes transient cell cycle exit after DNA damage.

E2F transcription factors control the expression of cell cycle genes. Cancers often demonstrate enhanced E2F target gene expression, which can be explained by increased percentages of replicating cells. However, we now demonstrate in human cancer biopsies that individual neoplastic cells display abnormally high levels of E2F-dependent transcription. To mimic this situation, we deleted the atypical E2F repressors (E2F7/8) in untransformed cells. Individual cells with elevated E2F-activity during S/G2-phase failed to exit the cell cycle after DNA damage and underwent mitosis. In contrast, wild type cells completed S-phase and then exit the cell cycle by activating the APC/CCdh1 via repression of the E2F-target Emi1. Strikingly, many arrested wildtype cells could eventually inactivate APC/CCdh1 to execute a second round of DNA replication and mitosis, thereby becoming tetraploid. Cells with elevated E2F-transcription fail to exit the cell cycle after DNA damage which potentially causes genomic instability, promotes malignant progression and reduces drug sensitivity.

cancer biology↗