A5070205069- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Hemoglobinopathies and Related Disorders
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Ubiquitin and proteasome pathways
- Animal Genetics and Reproduction
- Immune Cell Function and Interaction
- Viral gastroenteritis research and epidemiology
- Chromosomal and Genetic Variations
- interferon and immune responses
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- Chronic Lymphocytic Leukemia Research
- T-cell and B-cell Immunology
- Blood groups and transfusion
- Transgenic Plants and Applications
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Virus-based gene therapy research
- NF-κB Signaling Pathways
Inserm
2013-2025
Centre National de la Recherche Scientifique
2011-2025
Université de Montpellier
2020-2025
Laboratory of Excellence GR-Ex
2015-2025
Université Paris Cité
2016-2025
Institut de Génétique Moléculaire de Montpellier
2016-2024
Biologie Intégrée du Globule Rouge
2023
Institut des Maladies Génétiques Imagine
2023
Biogen (Switzerland)
2023
University Children’s Hospital Basel
2019
One of the complexes formed by hematopoietic transcription factor Gata1 is a complex with Ldb1 (LIM domain-binding protein 1) and Tal1 proteins. It known to be important for development differentiation erythroid cell lineage thought implicated in long-range interactions. Here, dynamics composition complex—in particular, binding negative regulators Eto2 Mtgr1—are studied, context their genome-wide targets. This shows that acts almost exclusively as an activator, very specific combination...
Genetic studies have identified common variants within the intergenic region (HBS1L-MYB) between GTP-binding elongation factor HBS1L and myeloblastosis oncogene MYB on chromosome 6q that are associated with elevated fetal hemoglobin (HbF) levels alterations of other clinically important human erythroid traits. It is unclear how these noncoding sequence affect multiple erythrocyte characteristics. Here, we determined several HBS1L-MYB regulatory elements occupied by key transcription factors...
Transcription steps are marked by different modifications of the C-terminal domain RNA polymerase II (RNAPII). Phosphorylation Ser5 and Ser7 cyclin-dependent kinase 7 (CDK7) as part TFIIH marks initiation, whereas phosphorylation Ser2 CDK9 elongation. These processes thought to take place in localized transcription foci nucleus, known “transcription factories,” but it has been argued that observed clusters/foci mere fixation or labeling artifacts. We show factories exist living cells...
The coupling of chromosome conformation capture (3C) with next-generation sequencing technologies enables the high-throughput detection long-range genomic interactions, via generation ligation products between DNA sequences, which are closely juxtaposed in vivo. These interactions involve promoter regions, enhancers and other regulatory structural elements chromosomes can reveal key details regulation gene expression. 3C-seq is a variant method for one chosen element (viewpoint) rest genome....
Abstract How transcription factors (TFs) cooperate within large protein complexes to allow rapid modulation of gene expression during development is still largely unknown. Here we show that the key haematopoietic LIM-domain-binding protein-1 (LDB1) TF complex contains several activator and repressor components together maintain an erythroid-specific programme primed for activation until differentiation induced. A combination proteomics, functional genomics in vivo studies presented here...
Abstract Despite its importance during viral or bacterial infections, transcriptional regulation of the interferon-β gene ( Ifnb1 ) in activated macrophages is only partially understood. Here we report that TRIM33 deficiency results high, sustained expression at late stages toll-like receptor-mediated activation but not fibroblasts. In macrophages, recruited by PU.1 to a conserved region, Control Element (ICE), located 15 kb upstream transcription start site. ICE constitutively interacts...
During B cell development, the precursor receptor (pre-BCR) checkpoint is thought to increase immunoglobulin κ light chain (Igκ) locus accessibility V(D)J recombinase. Accordingly, pre-B cells lacking pre-BCR signaling molecules Btk or Slp65 showed reduced germline Vκ transcription. To investigate whether modulates through enhancer-mediated Igκ topology, we performed chromosome conformation capture and sequencing analyses. These revealed that already in pro-B enhancers robustly interact with...
Acute megakaryoblastic leukemia of Down syndrome (DS-AMKL) is a model clonal evolution from preleukemic transient myeloproliferative disorder requiring both trisomy 21 (T21) and GATA1s mutation to driven by additional driver mutations. We modeled the megakaryocyte differentiation defect through stepwise gene editing GATA1s, SMC3+/–, MPLW515K, providing 20 different T21 or disomy (D21) induced pluripotent stem cell (iPSC) clones. profoundly reshaped iPSC-derived hematopoietic architecture...
Herpes simplex virus type 1 (HSV-1) infection induces profound nucleolar modifications at the functional and organizational levels, including invasion by several viral proteins. One of these proteins is US11, which exhibits different functions displays both cytoplasmic localization clear very similar to that major multifunctional protein nucleolin. To determine whether US11 interacts with nucleolin, we purified partners coimmunoprecipitations using a tagged protein, Flag-US11. From extracts...
Here, we show that transcription factors bound to regulatory sequences can be identified by purifying these unique directly from mammalian cells in vivo. Using targeted chromatin purification (TChP), a double-pull-down strategy with tetracycline-sensitive "hook" specific promoter, identify the repressed γ-globin gene-associated regions. After validation of binding, that, human primary erythroid cells, knockdown number induces gene expression. Reactivation expression ameliorates symptoms...
Abstract Genome-wide association studies (GWAS) have identified numerous genetic variants linked to human diseases, mostly located in non-coding regions of the genome, particularly putative enhancers. However, functional assessment GWAS has progressed at slow pace, since functions vast majority genomic enhancers not been defined, impeding interpretation disease-susceptibility variants. The HBS1L-MYB intergenic region harbors multiple SNPs associated with clinical erythroid parameters,...
Gfi-1B is a transcriptional repressor essential for the regulation of erythropoiesis and megakaryopoiesis. Here we identify p32, isoform, as erythroid differentiation. p32 generated by alternative splicing lacks two first zinc finger domains protein. Selective knock down compromises differentiation, whereas its ectopic expression induces in absence erythropoietin. isoform binds to target gene promoters associates with LSD1–CoREST complex more efficiently than major p37 isoform. Furthermore,...
// Anne-Sophie Gallouet 1, 2, 3, 4, 5 , Federica Ferri 5, 6, * Vanessa Petit Aude Parcelier Daniel Lewandowski Nathalie Gault Vilma Barroca Stéphanie Le Gras 6 Eric Soler 7 Frank Grosveld Irwin Davidson Paul-Henri Romeo 1 CEA/DRF/iRCM/LRTS, 92265 Fontenay-aux-Roses cedex, France 2 Inserm U967, 3 Université Paris-Diderot, Paris 7, 4 Paris-Sud, 11, Equipe labellisée Ligue contre le Cancer, Department of Functional Genomics and Institut de Génétique et Biologie Moléculaire Cellulaire,...
Abstract The detection of cytosolic dsDNA is tightly regulated to avoid pathological inflammatory responses. A major pathway involved in their relies on the cyclic GMP-AMP synthase (cGAS) that triggers activation Stimulator interferon genes (STING) which subsequently drives expression and type I Interferons (IFNs). Here, we show methyl-CpG-binding protein 2 (MECP2), a transcriptional regulator, controls dsDNA-associated We presence promotes MECP2 export from nucleus cytosol where it...