A5091488339- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Acute Lymphoblastic Leukemia research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related gene regulation
- CAR-T cell therapy research
- Histone Deacetylase Inhibitors Research
- Cancer-related molecular mechanisms research
- RNA and protein synthesis mechanisms
- Chronic Myeloid Leukemia Treatments
- T-cell and Retrovirus Studies
- Immunotherapy and Immune Responses
- Childhood Cancer Survivors' Quality of Life
- Immune responses and vaccinations
- CRISPR and Genetic Engineering
- Peptidase Inhibition and Analysis
- Animal Genetics and Reproduction
- Folate and B Vitamins Research
- Signaling Pathways in Disease
- Genetics, Bioinformatics, and Biomedical Research
- NF-κB Signaling Pathways
Inserm
2016-2025
Theories and Approaches of Genomic Complexity
2016-2025
Aix-Marseille Université
2015-2024
La Ligue Contre le Cancer
2018-2024
Marmara University
2024
Centre d’Immunologie de Marseille-Luminy
2001-2023
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2023
Polish Academy of Sciences
2023
University of Abou Bekr Belkaïd
2019
Centre National de la Recherche Scientifique
2002-2015
One clear hallmark of mammalian promoters is the presence CpG islands (CGIs) at more than two-thirds genes, whereas TATA boxes are only present a minority promoters. Using genome-wide approaches, we show that GC content and CGIs major promoter elements in cells, able to govern open chromatin conformation support paused transcription. First, define three classes with distinct transcriptional directionality pausing properties correlate their content. We further analyze direct influence on...
Purpose Early thymic precursor (ETP) acute lymphoblastic leukemia (ALL) is an immunophenotypically defined subgroup of T-cell ALL (T-ALL) associated with high rates intrinsic treatment resistance. Studies in children have shown that the negative prognostic impact chemotherapy resistance abrogated by implementation early response–based intensification strategies. Comparable data adults are lacking. Patients and Methods We performed comprehensive clinicobiologic, genetic, survival analyses a...
Cell-type specific regulation of gene expression requires the activation promoters by distal genomic elements defined as enhancers. The identification and characterization enhancers are challenging in mammals due to their genome complexity. Here we develop CapStarr-Seq, a novel high-throughput strategy quantitatively assess enhancer activity mammals. This approach couples capture regions interest previously developed Starr-seq technique. Extensive assessment CapStarr-seq demonstrates...
Characterization of the epigenetic landscape fundamentally contributes toward deciphering regulatory mechanisms that govern gene expression. However, despite an increasing flow newly generated data, no clear pattern chromatin modifications has so far been linked to specific modes transcriptional regulation. Here, we used high-throughput genomic data from CD4 + T lymphocytes provide a comprehensive analysis histone H3 lysine 4 dimethylation (H3K4me2) enrichment in regions surrounding start...
Abstract The large collections of ChIP-seq data rapidly accumulating in public warehouses provide genome-wide binding site maps for hundreds transcription factors (TFs). However, the extent regulatory occupancy space human genome has not yet been fully apprehended by integrating sets and combining it with ENCODE TFs map. To enable identification elements we have collected, analysed retained 395 available merged peaks covering a total 237 TFs. This enhanced repertoire complements refines...
Divergent transcription is a wide-spread phenomenon in mammals. For instance, short bidirectional transcripts are hallmark of active promoters, while longer can be detected antisense from genes conditions where the RNA degradation machinery inhibited. Moreover, many described long non-coding RNAs (lncRNAs) transcribed coding gene promoters. However, general significance divergent lncRNA/mRNA pair still poorly understood. Here, we used strand-specific RNA-seq with high sequencing depth to...
Gene targeting studies have shown that T cell receptor (TCR)-β gene expression and recombination are inhibited after deletion of an enhancer (Eβ) located at the 3′ end ∼500-kb TCR-β locus. Using knockout mouse models, we measured, different regions throughout locus, effects Eβ on molecular parameters believed to reflect epigenetic changes associated with control activation, including restriction endonuclease access chromosomal DNA, germline transcription, DNA methylation, histone H3...
To better understand why human neonates show a poor response to intracellular pathogens, we compared gene expression and histone modification profiles of neonatal naive CD8+ T cells with that their adult counterparts. We found lymphocytes have distinct epigenomic landscape associated lower genes involved in cell receptor (TCR) signaling cytotoxicity higher the cycle innate immunity. Functional studies corroborated are less cytotoxic, transcribe antimicrobial peptides, produce reactive oxygen...
Cell differentiation is accompanied by epigenetic changes leading to precise lineage definition and cell identity. Here we present a comprehensive resource of epigenomic data human T precursors along with an integrative analysis other hematopoietic populations. Although commitment large scale changes, observed that the majority distal regulatory elements are constitutively unmethylated throughout differentiation, irrespective their activation status. Among these, TCRA gene enhancer (Eα) in...
Post-translational histone modifications abound and regulate multiple nuclear processes. Most are targeted to the amino-terminal domains of histones. Here we report identification characterization acetylation lysine 56 within core domain H3. In crystal structure nucleosome, contacts DNA. Phenotypic analysis suggests that is critical for function it modulates formamide resistance, ultraviolet radiation sensitivity, sensitivity hydroxyurea. We show acetylated form H3 (H3-K56) present during...
Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this we compared DNA copy number aberrations (CNAs), promoter methylation, gene expression profiles, somatic mutations in nine selected genes, 32 tumors with those observed 156 BCs other molecular subtypes. Frequent CNAs included 8p11-p12 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23,...
Gene expression studies have consistently identified a HOXA-overexpressing cluster of T-cell acute lymphoblastic leukemias, but it is unclear whether these constitute homogeneous clinical entity, and the biological consequences HOXA overexpression not been systematically examined. We characterized biology outcome 55 HOXA-positive cases among 209 patients with adult leukemia uniformly treated during Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003 -2005 studies. had...
Promoters with enhancer activity have been described recently. In this point of view, we will discuss current findings highlighting the commonality type regulatory elements, their genetic and epigenetic characteristics, potential biological roles in regulation gene expression underlining molecular mechanisms.TSS: transcription start site; IFN: interferon; STARR-seq: Self-Transcribing Active Regulatory Region sequencing; MPRA: Massively Parallel Reporter Assay; ChIP: chromatin...
<ns4:p>The regulation of gene transcription in higher eukaryotes is accomplished through the involvement start site (TSS)-proximal (promoters) and -distal (enhancers) regulatory elements. It now well acknowledged that enhancer elements play an essential role during development cell differentiation, while genetic alterations these are a major cause human disease. Many strategies have been developed to identify characterize enhancers. Here, we discuss recent advances high-throughput approaches...
CD4+ T cells recognize antigens through their cell receptors (TCRs); however, additional signals involving costimulatory receptors, for example, CD28, are required proper activation. Alternative have been proposed, including members of the Toll-like receptor (TLR) family, such as TLR5 and TLR2. To understand molecular mechanism underlying a potential role TLR5, we generated detailed maps logical models TCR signaling pathways merged model cross-interactions between two pathways. Furthermore,...