Biology subjects

Robin, J.

Publications and source records attributed to Robin, J..

4 recordsLinked to original sources

bioRxiv2021

Specific telomere protection ensured by FOXO3a upon genotoxic stress and during aging

Longevity is determined by diverse signaling pathways including telomere protection and homeostasis master regulators like FOXO3a. We previously showed that the telomeric repeat binding factor 2 (TRF2) expression decreases with age in human skeletal muscle and that, surprisingly, its loss in myofibers does not trigger telomere deprotection. We reveal here that in TERF2-compromised myotubes, FOXO3a is recruited to telomeres where it acts as a protective factor against ATM-dependent DNA damage activation. Moreover, we show that FOXO3a-telomere association increases with age in human skeletal muscle biopsies. In mitotic fibroblasts, the telomere protective properties of FOXO3a are operative if the cells are treated with bleomycin. The telomere function of FOXO3a does not require its Forkhead DNA binding domain but the CR2C. Overall, these findings demonstrate a direct connection between two key longevity pathways, FOXO3a and telomere protection. This unveils an unexpected higher level of integration in the regulation of longevity signaling pathway.

cell biology↗

bioRxiv2018

Analysis of the 4q35 chromatin organization reveals distinct long-range interactions in patients affected with Facio-Scapulo-Humeral Dystrophy.

Facio-Scapulo Humeral dystrophy (FSHD) is the third most common myopathy, affecting 1 amongst 10,000 individuals (FSHD1, OMIM #158900). This autosomal dominant pathology is associated in 95% of cases with genetic and epigenetic alterations in the subtelomeric region at the extremity of the long arm of chromosome 4 (q arm). A large proportion of the remaining 5% of cases carry a mutation in the SMCHD1 gene (FSHD2, OMIM #158901). Here, we explored the 3D organization of the 4q35 locus by three-dimensions DNA in situ fluorescent hybridization (3D-FISH) in primary cells isolated from patients. We found that D4Z4 contractions and/or SMCHD1 mutations impact the spatial organization of the 4q35 region and trigger changes in the expression of different genes. Changes in gene expression was corroborated in muscle biopsies suggesting that long distance interaction modulate expression of a number of genes at the 4q35 locus in FSHD. Using induced pluripotent stem cells (hIPSC), we examined if chromatin organization is inherited or acquired during differentiation. Our data suggest that folding of the 4q35 region is modified upon differentiation. These results together with previous findings highlight the role of the D4Z4 repeat in the organization of chromatin and further indicate that the D4Z4-dependent 3D structure induces transcriptional changes of 4q35 genes expression.

cell biology↗

bioRxiv2017

Differential spatiotemporal representations along the hippocampal long axis in humans

Increased place field size and signal autocorrelation along the dorsoventral hippocampal axis in rodents are considered a fundamental aspect of hippocampal organization, yet such evidence is lacking in humans. Using fMRI, we report corresponding evidence of increasing neural similarity from posterior to anterior hippocampus (dorsoventral homologues) in humans. These findings help account for observed shifting in representational granularity, from global context (anterior) to local details (posterior), along the hippocampal axis.

neuroscience↗

bioRxiv2017

Long-term consolidation switches goal proximity coding from hippocampus to retrosplenial cortex

Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and Imperial College London students navigated virtual simulations of their own familiar campus (> 2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the proximity to the goal in the newly learned campus, but not in the familiar campus. By contrast retrosplenial cortex tracked the distance to the goal in the familiar campus, but not in the recently learned campus. These responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and help advance models of how neural circuits support navigation in novel and highly familiar environments.\n\nSignificance StatementHistorically, research on the hippocampal formation has focused on its role in long-term memory and navigation - often in isolation. No study to date has directly compared realistic navigation within familiar with recently learned environments, nor has it been explored how the neural substrates, along with computational codes, may change. In this study, we show for the first time, a shift from hippocampal to cortical coding of distance to a goal during active navigation. This study bridges the gap between memory consolidation and navigation, and paves the way for more functional and realistic understanding of the hippocampus.

neuroscience↗