A5027306694- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Estrogen and related hormone effects
- Cancer-related gene regulation
- Genetics and Neurodevelopmental Disorders
- TGF-β signaling in diseases
- RNA Research and Splicing
- DNA Repair Mechanisms
- 14-3-3 protein interactions
- Chronic Myeloid Leukemia Treatments
- Glioma Diagnosis and Treatment
- MRI in cancer diagnosis
- Mathematical Biology Tumor Growth
- Cytokine Signaling Pathways and Interactions
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- Cancer-related Molecular Pathways
- Histone Deacetylase Inhibitors Research
- Cancer and Skin Lesions
- Advanced Breast Cancer Therapies
- FOXO transcription factor regulation
- Cancer-related molecular mechanisms research
École Centrale de Nantes
2017-2024
Nantes Université
2018-2024
Inserm
2017-2024
Institut de Cancérologie de l'Ouest
2019-2021
Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers
2021
European Molecular Biology Laboratory
2016-2021
Cancer Research UK
2013-2020
University of Cambridge
2013-2020
Centre National de la Recherche Scientifique
2012-2020
Cancéropôle Grand Ouest
2020
Estrogen receptor-α (ER) is the driving transcription factor in most breast cancers, and its associated proteins can influence drug response, but direct methods for identifying interacting have been limited. We purified endogenous ER using an approach termed RIME (rapid immunoprecipitation mass spectrometry of proteins) discovered interactome under agonist- antagonist-liganded conditions cancer cells, revealing transcriptional networks cancer. The estrogen-enriched interactor GREB1, a...
Transcription factors (TFs) bind specifically to discrete regions of mammalian genomes called cis -regulatory elements. Among those are enhancers, which play key roles in regulation gene expression during development and differentiation. Despite the recognized central regulatory role exerted by chromatin control TF functions, much remains be learned regarding structure enhancers how it is established. Here, we have analyzed on a genomic-scale that recruit FOXA1, pioneer transcription factor...
Enhancers are developmentally controlled transcriptional regulatory regions whose activities modulated through histone modifications or variant deposition. In this study, we show by genome-wide mapping that the newly discovered deoxyribonucleic acid (DNA) modification 5-hydroxymethylcytosine (5hmC) is dynamically associated with transcription factor binding to distal sites during neural differentiation of mouse P19 cells and adipocyte 3T3-L1 cells. Functional annotation reveals gaining 5hmC...
Highlights•Mass spectrometry of chromatin-associated proteins with FOXA1 identifies MLL3•FOXA1 recruits MLL3 to deposit H3K4me1 on FOXA1-bound enhancers•MLL3 promotes ERα-dependent gene transcription and proliferation•GRHL2 co-occupies regions ERα, FOXA1, enhancersSummaryFOXA1 is a pioneer factor that binds enhancer are enriched in H3K4 mono- dimethylation (H3K4me1 H3K4me2). We performed rapid immunoprecipitation mass endogenous (RIME) screen ERα-positive MCF-7 breast cancer cells found...
ChIP-exonuclease (ChIP-exo) is a modified ChIP-seq approach for high resolution mapping of transcription factor DNA sites. We describe an Illumina-based ChIP-exo method which provides global improvement the data quality estrogen receptor (ER) ChIP and insights into motif structure key ER-associated factors. ER pioneer FoxA1 identifies protected with predictable 8 bp overhang from Forkhead motif, we term mesas. show that mesas occur in multiple cellular contexts exist as single or overlapping...
Significance Dynamic demethylation of histone residues plays a crucial role in the regulation gene expression. Lysine Specific Demethylase 1 (LSD1) can remove both transcriptionally permissive and repressive marks. How these activities are controlled is not clearly understood. Here, we show that estrogen-related receptor α (ERRα) induces LSD1 to erase marks vitro. Through such mechanism, ERRα commonly activate set transcriptional targets include genes involved cellular capacity invade...
Epigenetic mechanisms are believed to play key roles in the establishment of cell-specific transcription programs. Accordingly, modified bases 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been observed DNA genomic regulatory regions such as enhancers, oxidation 5mC into 5hmC by Ten-eleven translocation (TET) proteins correlates with enhancer activation. However, functional relationship between cytosine modifications chromatin architecture enhancers remains elusive. To gain...
Runt-related transcription factor 1 (RUNX1) is a well-known master regulator of hematopoietic lineages but its mechanisms action are still not fully understood. Here, we found that RUNX1 localizes on active chromatin together with Far Upstream Binding Protein (FUBP1) in human B-cell precursor lymphoblasts, and both factors interact the same transcriptional regulatory complex. FUBP1 localization identified c-KIT as common target gene. We characterized two regions, at +700 bp +30 kb within...
Cell identity relies on the cross-talk between genetics and epigenetics their impact gene expression. Oxidation of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) is first step an active DNA demethylation process occurring mainly at enhancers bodies and, as such, participates in processes governing cell normal pathological conditions. Although genetic alterations are well documented multiple myeloma (MM), epigenetic associated with this disease have not yet been thoroughly...
Estradiol signaling is ideally suited for analyzing the molecular and functional linkages between different layers of information directing transcriptional regulations: DNA sequence, chromatin modifications, spatial organization genome. Hence, estrogen receptor (ER) can bind at a distance from its target genes engages timely spatially coordinated processes to regulate their expression. In context regulation colinear genes, identifying which ER binding sites (ERBSs) given gene still remains...
Control of gene transcription relies on concomitant regulation by multiple transcriptional regulators (TRs). However, how recruitment a myriad TRs is orchestrated at cis -regulatory modules (CRMs) to account for coregulation specific biological pathways only partially understood. Here, we have used mouse liver CRMs involved in regulatory activities the hepatic TR, NR1H4 (FXR; farnesoid X receptor), as our model system tackle this question. Using integrative cistromic, epigenomic,...
The epigenetic mark 5-hydroxymethylcytosine (5hmC) is a cytosine modification that abundant in the central nervous system of mammals and which results from 5-methylcytosine oxidation by TET enzymes. Such suggested to play key roles regulation chromatin structure gene expression. However, its precise functions still remain poorly understood information about distribution non-mammalian species lacking. Here, 5hmC was investigated brain adult zebrafish, African claw frog, mouse comparative...
Leukemiaregulator of the Rag1 promoter and Rag1-Rag2 silencer antisilencer in mouse T-cells.We aimed to delineate causative link between presence RUNX1, ETV6-RUNX1 fusion protein RAG1 upregulation BCP-ALL.Our findings fulfill a missing step multi-hit model ETV6-RUNX1-related leukemogenesis gene aberrant activity.RAG1 RUNX1 transcripts levels are positively significantly correlated exclusively BCP-ALL compared other childhood (Fig. 1A, Supplementary Fig. S1A), suggesting
Abstract Background B Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) is the most common pediatric cancer. Identifying key players involved in proliferation of BCP-ALL cells crucial to propose new therapeutic targets. Runt Related Transcription Factor 1 (RUNX1) and Core-Binding Domain Alpha Subunit 2 Translocated To 3 (CBFA2T3, ETO2, MTG16) are master regulators hematopoiesis implicated leukemia. Methods We worked with mononuclear bone marrow patients’ cell lines, performed Chromatin...
Conventional techniques for single-base resolution mapping of epigenetic modifications DNA such as 5-hydroxymethylcytosine (5hmC) rely on the sequencing bisulfite-modified DNA. Here we present an alternative approach called SCL-exo which combines selective chemical labeling (SCL) 5hmC in genomic with exonuclease (exo) digestion bead-trapped modified molecules. Associated a straightforward bioinformatic analysis, this new procedure provides unbiased and fast method mark at high resolution....
MicroRNAs (miRNAs or miRs) play crucial roles in biological and pathological processes. Some miRNAs also appear as promising biomarkers therapeutic tools. However, the epitranscriptomic regulation of is not yet fully elucidated all their fields application. We report that adenosine methylation miR-200b-3p inhibits its repressive function toward mRNA targets such XIAP by blocking formation miRNA/3' UTR
Abstract Background Multiple myeloma (MM) is a heterogeneous plasma cell malignancy that remains challenging to cure. Global hypomethylation correlates with an aggressive phenotype of the disease, while hypermethylation observed at particular regions such as B cell-specific enhancers. The recently discovered active epigenetic mark 5-hydroxymethylCytosine (5hmC) may also play role in tumor biology; however, little known about its level and distribution myeloma. In this study, we investigated...
Abstract Background Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse chemotherapy resistance. Detailed understanding of the molecular underpinnings this disease essential to development personalised therapeutic strategies. Inhibitor differentiation 4 (ID4) helix-loop-helix transcriptional regulator required for mammary gland development. ID4 overexpressed in subset BLBC patients,...
Abstract FOXA1 is a pioneer factor that important in hormone dependent cancer cells to stabilise nuclear receptors, such as estrogen receptor (ER) chromatin. binds enhancers regions are enriched H3K4mono- and dimethylation (H3K4me1, H3K4me2) histone marks evidence suggests these requisite events for associate with initate subsequent gene expression events. However, exogenous of has been shown induce H3K4me1 H3K4me2 signal at enhancer elements the order functional importance not clear. We...
The interaction between mesenchymal stem cells (MSC) and Glioblastoma (GBM), although potentially of the highest importance, is ill-understood. This due, in part, to lack relevant experimental models. similarity vitro situations vivo situation can be improved by 3D co-culture as it reproduces key cell–cell interactions tumor microenvironment (TME) cancer cells. MSC Can acquired characteristics associated fibroblasts (CAF) being cultured with conditioned medium from GBM cultures thus are...
Abstract Glioblastoma multiforme (GBM), a highly aggressive brain tumor, frequently develops resistance to temozolomide (TMZ), the current standard chemotherapy. Our study investigates potential of combining TMZ with poly (ADP-ribose) polymerase inhibitor Olaparib (OLA) overcome resistance. Using in vitro models, including U251 cell lines and patient-derived GBM primary cultures, we demonstrate that OLA enhances efficacy by disrupting base excision repair potentiating DNA damage-induced...
This protocol is designed to obtain base-resolution information on the level of 5-hydroxymethylcytosine (5hmC) in CpGs without need for bisulfite modification. It relies (i) capture hydroxymethylated sequences by a procedure known as 'selective chemical labeling' (see Szulwach et al., 2012 ) and (ii) digestion captured DNA exonucleases. After Illumina sequencing digested fragments, an ad hoc bioinformatic pipeline extracts further downstream analysis.