Biology subjects

Foldes, T.

Publications and source records attributed to Foldes, T..

4 recordsLinked to original sources

bioRxiv2025

Condensin Accelerates Long-Range Intra-Chromosomal Interactions

The 3D genome organization plays a key role in regulating interactions among chromosomal loci. While Chromosome Conformation Capture (3C)-based methods have provided static snapshots of chromatin architecture, the kinetics of chromosomal encounters in live cells remain poorly characterized. In this study, we employ Chemically Induced Chromosomal Interaction (CICI) to measure encounter times between multiple loci pairs in G1-arrested budding yeast. Our results show that chromosome motion closely follows the Rouse polymer model, with similar diffusion parameters at all tested loci. Surprisingly, we find that long-range intra-chromosomal encounters occur significantly faster than inter-chromosomal encounters at similar 3D distances. Using targeted depletion experiments, we identify condensin, but not cohesin, as the complex responsible for these rapid intra-chromosomal interactions. This is further supported by Hi-C analysis, which reveals that condensin promotes long-distance intra-chromosomal interactions in G1 yeast. Through polymer simulations, we estimate that condensin extrudes chromatin at [~]2 kb/s with a density of one complex per 1-2 Mb and a processivity of 120-220 kb. These findings uncover a novel role for condensin in shaping the interphase genome organization and provide new insights into chromosomal search dynamics in vivo.

molecular biology↗

bioRxiv2024

Smc5/6 association with microtubules controls dynamic pericentromeric chromatin folding

Centromeres and pericentromeres are specialized chromatin regions essential for accurate chromosome segregation. Smc5/6, which localizes at pericentromeres, can bind microtubules, yet its role in chromatin folding is unclear. Here, we investigate the functional relevance of Smc5/6- microtubule binding in yeast, by targeting two lysines (K624, K631) within the Smc5 hinge domain known to mediate this binding. Using high-temporal-resolution imaging, polymer modelling, and in vitro approaches with a separation-of-function mutant smc5-2KE, we demonstrate that microtubules binding by Smc5/6 constrains chromatin dynamics and promotes pericentromeric folding. The smc5-2KE mutant, combined with a hypomorphic kinetochore mutant (Mtw1-3xGFP), leads to spindle and cytokinesis defects and triggers the spindle checkpoint. Furthermore, homologous recombination repair in pericentromeres is compromised. Overall, our findings indicate that Smc5/6 - microtubules association safeguard pericentromeric architecture and genome stability during mitosis.

cell biology↗

bioRxiv2024

Exploring the roles of memory replay in targeted memory reactivation and birdsong development: Insights from computational models of complementary learning systems

Replay facilitates memory consolidation in both biological and artificial systems. Using the complementary learning systems (CLS) framework, we study replay in both humans and birds through computational modelling. We investigate impacts of replay triggered by targeted memory reactivation during sleep and experiments examining how sleep affects the development of birdsong in young songbirds. We show that qualitatively realistic sleep effects can be captured by highly abstracted, idealised CLS models. Our modelling sheds theoretical insights on the mechanisms underlying both strengthening and weakening effects of targeted memory reactivation, and supports the empirical hypothesis that replay drives overnight performance deterioration and correlates positively with the final performance in birdsong development. Author summaryTaking a computational approach, we investigated the roles of memory replay in two complementary learning systems (CLS) models capturing realistic sleep effects observed in two real-life experiments on targeted memory reactivation (TMR) and birdsong development respectively. Our two CLS models are abstract and identical in architecture, and they are distinct in terms of where replay is generated. While the TMR model produces replay samples using its hippocampus, the birdsong model does so using the sensorimotor cortex. We found that certain TMR effects could characterise different TMR models, which might account for individual differences in human subjects. The results of the birdsong model support the idea that the dramatic overnight oscillations in performance accuracy which are observed during birdsong development are mainly driven by memory replay, and that long-term performance gain can be achieved despite short-term performance deterioration during the early nights of development. As we studied the two experiments using the unified CLS framework, we discuss how replay contributes to sleep-dependent performance changes from the perspective of systems consolidation.

neuroscience↗

bioRxiv2024

Disarming emotional memories using Targeted Memory Reactivation during Rapid Eye Movement sleep

Emotional responses are dampened across sleep, and this is thought to be mediated by neural reactivation during Rapid Eye Movement (REM) Sleep. Such reactivation can be triggered by targeted memory reactivation (TMR), a technique in which a tone previously associated with a memory during wake is re-presented during subsequent sleep. Prior work has shown that TMR in REM reduces arousal responses to negative stimuli. The present study builds on this by measuring autonomic responses and brain activity as well as behaviour. Participants rated the arousal of 48 affective images, paired with semantically matching sounds. Half of these sounds were cued during REM in the subsequent overnight sleep cycle. Participants rated the images in a Magnetic Resonance Imaging (MRI) scanner with pulse oximetry 48 hours after encoding, and again after two weeks. Results showed that TMR during REM was also associated with reduced brain activity in the two primary nodes of the Salience Network (SN): the Anterior Insula and dorsal Anterior Cingulate Cortex (dACC), as well as the orbitofrontal cortex, subgenual cingulate, and left amygdala, all of which are known to be important for emotional processing. TMR markedly reduced the emotional heart rate deceleration (HRD) response, and also reduced subjective arousal ratings for highly arousing images, while increasing ratings for less arousing images. We conclude that REM TMR can facilitate a decrease in physiological and neurological responses to arousal. These findings have potential implications for the use of TMR in treatment of depression and anxiety disorders. HighlightsO_LITMR in REM sleep reduces Salience Network responses to emotional pictures. C_LIO_LITMR in REM sleep reduces heart rate deceleration to emotional pictures. C_LIO_LITMR in REM sleep reduces subjective arousal ratings of highly arousing images. C_LIO_LITMR in REM sleep provides a promising potential avenue for treatment of PTSD. C_LI

neuroscience↗