Schalbetter, S. | bioRxiv Science

bioRxiv2025

Condensin chromatin association is regulated by SMC head and hinge engagement and phosphorylation

The SMC condensin complex is essential for normal mitotic chromosome structure in eukaryotes. Here, we analyze how ATP binding and hydrolysis, SMC hinge stability, and condensin subunit phosphorylation influence condensin chromatin association in budding yeast. We show that mutations predicted to destabilize ATP binding and head-to-head engagement impair condensin chromatin association as assayed by ChIP. In contrast, mutations that inactivate the complex by destabilizing the hinge domain interaction, enhance chromatin association at known condensin loading sites. We find that condensin phosphorylation is enriched in enzymatic states associated with elevated chromatin binding. Moreover, phosphorylation and Aurora/Ipl1 kinase activity--but not Cdc5--are required to maintain condensin association with mitotic chromatin in early metaphase.

molecular biology↗

bioRxiv2023

Microglia undergo transcriptional, translational and functional adaptations to dark and light phases in laboratory mice

Microglia cells are increasingly recognized to contribute to brain health and disease. Preclinical studies using laboratory rodents are essential to advance our understanding of the physiological and pathophysiological functions of these cells in the central nervous system. Rodents are nocturnal animals, and they are mostly maintained in a defined light-dark cycle within animal facilities, with many laboratories investigating microglial molecular and functional profiles during the animals light (sleep) phase. However, only a few studies have considered possible differences in microglial functions between the active and sleep phases. Based on initial evidence suggesting that microglial intrinsic clock genes can affect their phenotype, we sought to investigate differences in transcriptional, proteotype and functional profiles of microglia between light (sleep) and dark (active) phases, and how these changes are affected in pathological models. We found marked transcriptional and proteotype differences between microglia harvested during the light or dark phase. Amongst others, these differences related to genes and proteins associated with immune responses, motility, and phagocytosis, which were reflected by functional alterations in microglial synaptic pruning and response to bacterial stimuli. Possibly accounting for such circadian changes, we found RNA and protein regulation in SWI/SNF and NuRD chromatin remodeling complexes between light and dark phases. Importantly, we show that microglial circadian transcriptional changes are impaired in a model of immune-mediated neurodevelopmental disorders. Our findings emphasize the importance of considering circadian factors in studying microglial cells and indicate that implementing a circadian perspective is pivotal for advancing our understanding of their physiological and pathophysiological roles in brain health and disease. This may also open novel avenues towards therapeutic strategies for modulating microglial functions during specific windows of the active or sleep phase.

neuroscience↗