Ets-1 interacts through a similar binding interface with Ku70 and Poly (ADP-Ribose) Polymerase-1

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Médiateur et facteurs NER lors de l'initiation de la transcription

The synthesis of messenger RNA is a highly regulated process. During transcription initiation, a large number of proteins are recruited to gene promoter, including the RNA polymerase II, general transcription factors, co-activators, chromatin remodellers and the Mediator complex. Some DNA repair factors from the NER pathway are also recruited. Using cells derived from patients bearing mutations in either MED12 gene or XPC gene, we studied the roles of such proteins in transcription. MED12 patients are mostly characterised by intellectual disability and developmental delay. We showed that MED12 is implicated in the transcription regulation of immediate early genes like JUN, known for its role in neurological development and neuronal plasticity. JUN expression is markedly altered by MED12 mutations. We also showed that the position of the mutation influences this alteration, bringing possible explanation for inter-patients symptom variability. Meanwhile, XPC patients are mostly characterized by photosensitivity. We showed that XPC protein, which engages one of the NER pathways, is implicated in chromatin post-translational modification. Together with E2F1, it helps the recruitment of GCN5 acetyl-transferase to promoter of a certain set of genes. On the promoter, GCN5 notably cooperates with TFIIH to modify the chromatin environment during transcription initiation. In addition to help the comprehension of the transcription mechanisms, these results bring knew insight into the aetiology of mutations associated diseases.La synthèse d’ARN messagers résulte d’une cascade d’évènements temporellement et spatialement orchestrée. Au moment de l’initiation de la transcription, divers facteurs tels que les facteurs généraux de transcription, le complexe Médiateur, des co-activateurs, des facteurs de remodelage de la chromatine ainsi que l’ARN polymérase II sont recrutés au niveau de la région promotrice du gène. Certains facteurs de la voie NER de réparation de l’ADN sont également recrutés. En utilisant des cellules de patients porteurs de mutations dans les gènes MED12 (sous-unité du Médiateur) ou XPC (facteur initiant la voie NER), nous avons pu étudier le rôle de ces protéines dans la transcription. Les patients MED12 sont notamment caractérisés par une lourde déficience intellectuelle et des malformations congénitales. Nous avons montré que MED12 est impliqué dans le contrôle de certains gènes de réponse immédiate comme JUN, qui contribue notamment au développent et à la plasticité cérébrale. L’expression de ce dernier est affectée par les mutations de MED12, mais différemment en fonction de la position de la mutation, apportant une possible indication sur l’origine des variations phénotypiques observées chez les patients. En parallèle, les patients XPC se caractérisent par une forte photosensibilité. Nous avons montré que la protéine XPC, en collaboration avec le facteur E2F1, est impliquée dans le recrutement de l’histone acetyl-transférase GCN5 au niveau du promoteur d’un certain nombre de gènes. Cette dernière permet notamment l’a modification de l’environnement chromatinien, en coopération avec le facteur général de transcription TFIIH et participe ainsi à l’initiation de la transcription. En plus d’approfondir la compréhension des mécanismes régissant la transcription, ces résultats ont permis de mieux comprendre l’étiologie des maladies associées aux mutations

Cytokinin Sensing in Bacteria

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Megaviruses: an involvement in phytohormone receptor gene transfer in brown algae?

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Cytokinin and Ethylene Cell Signaling Pathways from Prokaryotes to Eukaryotes

International audienceCytokinins (CKs) and ethylene (ET) are among the most ancient organic chemicals on Earth. A wide range of organisms including plants, algae, fungi, amoebae, and bacteria use these substances as signaling molecules to regulate cellular processes. Because of their ancestral origin and ubiquitous occurrence, CKs and ET are also considered to be ideal molecules for inter-kingdom communication. Their signal transduction pathways were first historically deciphered in plants and are related to the two-component systems, using histidine kinases as primary sensors. Paradoxically, although CKs and ET serve as signaling molecules in different kingdoms, it has been supposed for a long time that the canonical CK and ET signaling pathways are restricted to terrestrial plants. These considerations have now been called into question following the identification over recent years of genes encoding CK and ET receptor homologs in many other lineages within the tree of life. These advances shed new light on the dissemination and evolution of these hormones as both intra-and inter-specific communication molecules in prokaryotic and eukaryotic organisms

Are Histidine Kinases of Arbuscular Mycorrhizal Fungi Involved in the Response to Ethylene and Cytokinins?

International audienceSignals are exchanged at all stages of the arbuscular mycorrhizal (AM) symbiosis between fungi and their host plants. Root-exuded strigolactones are well-known early symbiotic cues, but the role of other phytohormones as interkingdom signals has seldom been investigated. Here we focus on ethylene and cytokinins, for which candidate receptors have been identified in the genome of the AM fungus Rhizophagus irregularis. Ethylene is known from the literature to affect asymbiotic development of AM fungi, and in the present study, we found that three cytokinin forms could stimulate spore germination in R. irregularis. Heterologous complementation of a Saccharomyces cerevisiae mutant strain with the candidate ethylene receptor RiHHK6 suggested that this protein can sense and transduce an ethylene signal. Accordingly, its N-terminal domain expressed in Pichia pastoris displayed saturable binding to radiolabeled ethylene. Thus, RiHHK6 displays the expected characteristics of an ethylene receptor. In contrast, the candidate cytokinin receptor RiHHK7 did not complement the S. cerevisiae mutant strain or Medicago truncatula cytokinin receptor mutants and seemed unable to bind cytokinins, suggesting that another receptor is involved in the perception of these phytohormones. Taken together, our results support the hypothesis that AM fungi respond to a range of phytohormones and that these compounds bear multiple functions in the rhizosphere beyond their known roles as internal plant developmental regulators. Our analysis of two phytohormone receptor candidates also sheds new light on the possible perception mechanisms in AM fungi

Species distribution and antifungal susceptibility of Aspergillus clinical isolates in Lebanon

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