A5062071694- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Gene expression and cancer classification
- Plant Molecular Biology Research
- Bacteriophages and microbial interactions
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- Genomics and Phylogenetic Studies
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Chemical Reactions and Isotopes
- Single-cell and spatial transcriptomics
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Machine Learning in Bioinformatics
Génétique Physiologie et Systèmes d'Elevage
2013-2024
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2013-2024
Université Paris Cité
2014-2023
Institut Jacques Monod
2014-2023
Centre National de la Recherche Scientifique
2016-2023
Howard Hughes Medical Institute
2016-2022
University of Massachusetts Chan Medical School
2016-2022
Fera Science (United Kingdom)
2019
Oncogenes are activated through well-known chromosomal alterations such as gene fusion, translocation, and focal amplification. In light of recent evidence that the control key genes depends on chromosome structures called insulated neighborhoods, we investigated whether proto-oncogenes occur within these oncogene activation can via disruption neighborhood boundaries in cancer cells. We mapped neighborhoods T cell acute lymphoblastic leukemia (T-ALL) found tumor genomes contain recurrent...
The cohesin complex plays an essential role in chromosome maintenance and transcriptional regulation. Recurrent somatic mutations the are frequent genetic drivers cancer, including myelodysplastic syndromes (MDS) acute myeloid leukemia (AML). Here, using dependency screens of stromal antigen 2-mutant (STAG2-mutant) AML, we identified DNA damage repair replication as dependencies cohesin-mutant cells. We demonstrated increased levels sensitivity cells to poly(ADP-ribose) polymerase (PARP)...
Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated involvement three elements enriched at gene promoters replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), histone variant H2A.Z, firing origins vertebrates. We show that two pG4s on same DNA strand (dimeric...
The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. transcription factor CTCF is a candidate regulator chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that absolutely and dose-dependently required for looping between target sites segmental organization into topologically associating domains (TADs). Restoring reinstates proper architecture on altered chromosomes, indicating powerful instructive...
SUMMARY Cohesin-mediated loop extrusion folds interphase chromosomes at the ten to hundreds kilobases scale. This process produces structural features such as loops and topologically associating domains. We identify three types of cis -elements that define chromatin folding landscape generated by extrusion. First, CTCF sites form boundaries stalling extruding cohesin, shown before. Second, transcription termination acting cohesin unloading sites. RNA polymerase II contributes boundary...
Abstract The genome is hierarchically organized in 3D space and its architecture altered differentiation, development disease. Some of the general principles that determine global organization have been established. However, extent nature cell-to-cell cell-intrinsic variability are poorly characterized. Here, we systematically probe heterogeneity human fibroblasts by combining high-resolution Hi-C datasets high-throughput imaging. Optical mapping several hundred interaction pairs at single...
Article16 September 2020Open Access Transparent process Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain Caroline Brossas CNRS, Institut Jacques Monod, Equipe Labellisée Association Pour la Recherche sur le Cancer, Université de Paris, France Search for more papers by this author Anne-Laure Valton Department Biochemistry and Molecular Pharmacology, Program in Systems Biology, University Massachusetts Medical School,...
Summary Chromosome folding is extensively modulated as cells progress through the cell cycle. During mitosis, condensin complexes fold chromosomes in helically arranged nested loop arrays. In interphase, cohesin complex generates loops that can be stalled at CTCF sites leading to positioned and topologically associating domains (TADs), while a separate process of compartmentalization drives spatial segregation active inactive chromatin domains. We used synchronized cultures determine how...
Abstract Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated involvement three elements enriched at gene promoters replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), histone variant H2A.Z, firing origins vertebrates. We show that two pG4s on same DNA strand...