A5041312363- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Gallbladder and Bile Duct Disorders
- RNA Research and Splicing
- Pharmaceutical Practices and Patient Outcomes
- Cancer therapeutics and mechanisms
- Hepatitis C virus research
- Pharmaceutical studies and practices
- DNA Repair Mechanisms
- Gastrointestinal disorders and treatments
- Cancer-related gene regulation
- RNA regulation and disease
- MicroRNA in disease regulation
- Liver Disease Diagnosis and Treatment
- Esophageal and GI Pathology
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Pediatric Hepatobiliary Diseases and Treatments
- Biliary and Gastrointestinal Fistulas
- Safe Handling of Antineoplastic Drugs
- Mechanisms of cancer metastasis
- Oral health in cancer treatment
- Telomeres, Telomerase, and Senescence
Hospital General De Zona
2025
Mexican Social Security Institute
2025
Centre National de la Recherche Scientifique
2006-2024
Santa Lucía University General Hospital
2018-2024
Université de Toulouse
2010-2024
Université Toulouse III - Paul Sabatier
2008-2024
Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération
2008-2022
La Ligue Contre le Cancer
2001-2022
Hôpital Beaujon
2010
National Institutes of Health
2006-2008
Ataxia telangiectasia mutated (ATM), the deficiency of which causes a severe neurodegenerative disease, is crucial mediator for DNA damage response (DDR). As neurons have high rates transcription that require topoisomerase I (TOP1), we investigated whether TOP1 cleavage complexes (TOP1cc)—which are potent transcription‐blocking lesions—also produce transcription‐dependent double‐strand breaks (DSBs) with ATM activation. We show induction DSBs and DDR activation in post‐mitotic primary...
The E2F transcription factor controls the cell cycle-dependent expression of many S-phase-specific genes. Transcriptional repression these genes in G(0) and at beginning G(1) by retinoblasma protein Rb is crucial for proper control proliferation. has been proposed to function, least part, through recruitment histone deacetylases. However, recent results indicate that other chromatin-modifying enzymes are likely be involved. Here, we show also interacts with a methyltransferase, which...
Abstract Background The function of the non-coding portion human genome remains one most important questions our time. Its vast complexity is exemplified by recent identification an unusual and notable component transcriptome - very long intergenic RNAs, termed vlincRNAs. Results Here we identify 2,147 vlincRNAs covering 10 percent genome. We show they are present not only in cancerous cells, but also primary cells normal tissues, controlled canonical promoters. Furthermore, vlincRNA...
TDP1 removes transcription-blocking topoisomerase I cleavage complexes (TOP1ccs), and its inactivating H493R mutation causes the neurodegenerative syndrome SCAN1. However, molecular mechanism underlying SCAN1 phenotype is unclear. Here, we generate human cell models using CRISPR-Cas9 show that they accumulate TOP1ccs along with changes in gene expression genomic distribution of R-loops. cells also transcriptional DNA double-strand breaks (DSBs) specifically G1 population due to increased DSB...
The retinoblastoma susceptibility gene product, the Rb protein, is a key regulator of mammalian cell proliferation. One major targets S phase inducing E2F transcription factor. Once bound to E2F, represses expression E2F-regulated genes. Transcriptional repression by believed be crucial for proper control growth. Recently, we and others showed that through recruitment histone deacetylase. Interestingly, show here Rb-associated deacetylase complex could deacetylate polynucleosomal substrates,...
Abstract Non-coding RNAs (ncRNAs) play major roles in proper chromatin organization and function. Senescence, a strong anti-proliferative process anticancer barrier, is associated with dramatic reorganization heterochromatin foci. Here we analyze strand-specific transcriptome changes during oncogene-induced human senescence. Strikingly, while differentially expressed are mostly repressed senescence, ncRNAs belonging to the recently described vlincRNA (very long intergenic ncRNA) class mainly...
Antisense RNAs are non-coding that can regulate their corresponding sense and generally produced from specific promoters. We uncover here a family of antisense RNAs, named START during cellular senescence by transcriptional read-through at convergent protein-coding genes. Importantly, repress the expression RNAs. In proliferative cells, we found Pol II elongation rate is limited downstream TTS loci, allowing transcription termination to occur before reaches genes, thus preventing RNA...
The H2A.Z histone variant plays major roles in the control of gene expression. In human, is encoded by two genes expressing isoforms, H2A.Z.1 and H2A.Z.2 differing three amino acids. Here, we undertook an integrated analysis their functions expression using endogenously-tagged proteins. RNA-Seq untransformed cells showed that they can regulate both distinct overlapping sets positively or negatively a context-dependent manner. Furthermore, have similar antagonistic function depending on...
AbstractEpigenetic marks that specify silent heterochromatic domains in eucaryotic genomes include methylation of histone H3 lysine 9. Strikingly, active loci the vicinity are sometimes characterized by acetylation 9, suggesting balance between these two competitive modifications is important for establishment specific chromatin structures. Some euchromatic genes, targeted retinoblastoma protein Rb, also believed to be regulated 9 methylation. Here, we study dihydrofolate reductase promoter,...
Biliary mucinous cystic neoplasms (BMCNs) are rare tumors that account for less than 5% of lesions in the biliary tract, predominantly affecting middle-aged women and often presenting as asymptomatic or with nonspecific symptoms. The primary treatment is surgical resection negative margins. We report a case grade I non-invasive BMCN was completely extrahepatic, treated hepaticojejunostomy. A 42-year-old female history type 2 diabetes referred multiple episodes acute cholangitis. Magnetic...
The product of the retinoblastoma susceptibility gene, Rb protein, functions partly through transcriptional repression E2F-regulated genes. Repression by is mediated, at least in part, a histone deacetylase complex, whose enzymatic activity relies on HDAC1, HDAC2 or HDAC3. Recently, we have shown that Rb-associated complex contains RbAp48 which interacts with HDAC1 and HDAC2. could favour deacetylation histones since it binds directly to H4. In agreement that, show E2F requires presence...
Functionality of the non-coding transcripts encoded by human genome is coveted goal modern genomics research. While commonly relied on classical methods forward genetics, integration different datasets in a global Systems Biology fashion presents more productive avenue achieving this very complex aim. Here we report application Biology-based approach to dissect functionality newly identified vast class long intergenic (vlinc) RNAs. Using highly quantitative FANTOM5 CAGE dataset, show that...
Abstract Background The majority of the human genome is transcribed in form long non-coding (lnc) RNAs. While these transcripts have attracted considerable interest, their molecular mechanisms function and biological significance remain controversial. One main reasons behind this lies significant challenges posed by lncRNAs requiring development novel methods concepts to unravel functionality. Existing often lack cross-validation independent confirmation different methodologies therefore...
Long non-coding RNAs (ncRNAs) are major regulators of gene expression and cell fate. The INK4 locus encodes the tumour suppressor proteins p15INK4b, p16INK4a p14ARF required for cycle arrest whose increases during senescence. ANRIL is a ncRNA antisense to p15 gene. In proliferative cells, prevents senescence by repressing genes through recruitment Polycomb-group proteins. models replicative RASval12 oncogene-induced (OIS), Polycomb decreases, thus allowing derepression. Here, we found in...
Transcriptional gene silencing by small interfering RNAs (siRNAs) has been widely described in various species, including plants and yeast. In mammals, its extent remains somewhat debated. Previous studies showed that siRNAs targeting promoters could induce the of targeted promoter, although involvement off-target mechanisms was also suggested. Here, using nascent RNA capture polymerase II chromatin immunoprecipitation, we show a chromatin-associated noncoding induced transcriptional...
La structure de la chromatine joue un role majeur dans le controle mecanismes, comme transcription, qui necessitent l'acces a double helice d'ADN. Cette peut notamment etre controlee par des modifications post-traductionnelles histones nucleosomales. Le crucial l'acetylation ou phosphorylation l'expression genique est maintenant bien etabli. Un certain nombre resultats tres nouveaux mettent en evidence l'importance d'une autre modification posttraductionnelle histones, methylation. revue se...