ORCID Profile
0000-0001-5865-8372
Current Organisation
INSERM
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Oxford University Press (OUP)
Date: 30-01-2019
DOI: 10.1093/NAR/GKZ005
Publisher: Cold Spring Harbor Laboratory
Date: 10-2022
DOI: 10.1101/2022.09.30.510336
Abstract: Among epigenetic modifiers, telomeres, represent attractive modulators of the genome in part through position effects. Telomere Position Effect – Over Long Distances (TPE-OLD) modulates genes expression by changes in telomere-dependent long-distance loops, with a reach of 10Mb from a telomere. However, TPE-OLD remains poorly defined. To gain further insights into the genome-wide impact of telomere length on genomic and epigenomic regulation through TPE-OLD, we used cells with controlled telomere length combined to a genome wide transcriptome and methylome analysis. By integrating omics data, we identified a common cis -acting motif that behaves as an insulator or enhancer. Using reporter assays integrating this element, we uncovered the trans partners regulating this activity. Further exploiting our cellular model, we observed the depletion of one candidate factor, RBPJ, at TPE-OLD associated loci upon telomere shortening. We concluded that, at the genome-wide level, TPE-OLD is relayed by RBPJ binding Alu-like elements to telomeres that acts as enhancers. In response to external stimuli ( i . e ., Aging), TPE-OLD might act by coordinating telomere length to the action of Alu newly evolved enhancers in association with RBPJ.
Publisher: Life Science Alliance, LLC
Date: 14-09-2022
Abstract: Progeroid syndromes are rare genetic diseases with most of autosomal dominant transmission, the prevalence of which is less than 1/10,000,000. These syndromes caused by mutations in the LMNA gene encoding A-type lamins belong to a group of disorders called laminopathies. Lamins are implicated in the architecture and function of the nucleus and chromatin. Patients affected with progeroid laminopathies display accelerated aging of mesenchymal stem cells (MSCs)–derived tissues associated with nuclear morphological abnormalities. To identify pathways altered in progeroid patients’ MSCs, we used induced pluripotent stem cells (hiPSCs) from patients affected with classical Hutchinson–Gilford progeria syndrome (HGPS, c.1824C T—p.G608G), HGPS-like syndrome (HGPS-L c.1868C G—p.T623S) associated with farnesylated prelamin A accumulation, or atypical progeroid syndromes (APS homozygous c.1583C T—p.T528M heterozygous c.1762T C—p.C588R compound heterozygous c.1583C T and c.1619T C—p.T528M and p.M540T) without progerin accumulation. By comparative analysis of the transcriptome and methylome of hiPSC-derived MSCs, we found that patient’s MSCs display specific DNA methylation patterns and modulated transcription at early stages of differentiation. We further explored selected biological processes deregulated in the presence of LMNA variants and confirmed alterations of age-related pathways during MSC differentiation. In particular, we report the presence of an altered mitochondrial pattern an increased response to double-strand DNA damage and telomere erosion in HGPS, HGPS-L, and APS MSCs, suggesting converging pathways, independent of progerin accumulation, but a distinct DNA methylation profile in HGPS and HGPS-L compared with APS cells.
Location: United States of America
Location: United States of America
No related grants have been discovered for Jerome Robin.