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Répercussion Du Développement Année 2020 RÉPERCUSSION DU DÉVELOPPEMENT MORPHOCINÉTIQUE PRÉCOCE SUR LA TRANSITION MATERNO-EMBRYONNAIRE : COMPARAISON DES TRANSCRIPTOMES D’EMBRYONS BOVINS AU STADE 16-32 CELLULES THÈSE pour obtenir le grade de DOCTEUR VÉTÉRINAIRE présentée et soutenue publiquement devant LA FACULTÉ DE MÉDECINE DE CRÉTEIL le 29 septembre 2020 par Audrey, Colette, Géraldine TESTE née le 7 janvier 1995 à Toulouse (Haute-Garonne) sous la direction de Alline DE PAULA REIS Président du jury : Pr Alexandre DE LA TAILLE Professeur à la Faculté de Médecine de CRÉTEIL 1er Assesseur : Dr Alline DE PAULA REIS Maître de Conférences à l’EnvA 2nd Assesseur : Dr Lucie CHEVALLIER Maître de Conférences à l’EnvA Remerciements Au Président du Jury de cette thèse, Professeur à la Faculté de Médecine de Créteil, Qui nous a fait l’honneur d’accepter la présidence du jury de cette thèse, Hommage respectueux. À Mme Alline DE PAULA REIS, Maitre de conférences à l’EnvA, Pour avoir placé votre confiance en moi pour l’écriture de cette thèse dont le sujet vous tenait tant à cœur et pour m’avoir épaulé, aiguillé, rassuré tant de fois au cours de ce travail difficile, pour n’avoir jamais baissé les bras et pour votre bonne humeur perpétuelle, Mes plus sincères remerciements. À Mme Lucie CHEVALLIER, Maitre de conférences à l’EnvA, Pour avoir acceptée d’être l’assesseure de cette thèse, pour votre relecture consciencieuse et pour vos remarques qui m’ont beaucoup touchée et rassurée sur mon travail, Sincères remerciements. À Véronique DURANTHON, Directrice de recherche, Catherine ARCHILLA, Assistante ingénieur, Luc JOUNEAU, Ingénieur de recherche et Sophie CALDERARI, Chargée de recherche à l’INRAE, Pour votre disponibilité, ainsi que pour vos conseils et votre aide précieuse dans l’analyse des résultats de cette thèse, Sincères remerciements. À mes parents, Pour m’avoir emmenée là où j’en suis aujourd’hui, pour m’avoir donné tant d’amour et pour ce lien indéfectible qui nous unit. À ma famille, Pour vos encouragements, votre écoute, votre soutien et votre amour. À Aurélien, Pour avoir accepté de m’aimer inconditionnellement. À mes amis, Qui m’ont apporté tant de bonheur au quotidien et m’ont permis de me donner à fond, pour avoir teinté ma vie de rires, d’aventures et de souvenirs incroyables. Table des matières Table des matières..................................................................................................................... 1 Liste des figures ......................................................................................................................... 5 Liste des tableaux ...................................................................................................................... 7 Liste des abréviations ................................................................................................................ 9 Introduction .............................................................................................................................19 Première partie : Bibliographie .................................................................................................21 I. Le développement embryonnaire précoce chez les bovins ............................................................ 21 1. L’ovocyte avant la fécondation ........................................................................................................................ 21 a. La maturation nucléaire de l’ovocyte ................................................................................................................... 21 b. La maturation cytoplasmique de l’ovocyte ........................................................................................................... 22 c. La maturation moléculaire de l’ovocyte ............................................................................................................... 22 Les ARN ............................................................................................................................................................ 23 Les protéines .................................................................................................................................................... 23 d. La régulation des ARN maternels ......................................................................................................................... 23 La polyadénylation et le masquage des ARNm ................................................................................................ 24 Le démasquage : initiation de la traduction dépendante du CPE ..................................................................... 24 La régulation temporelle du démasquage ........................................................................................................ 26 La déadénylation des ARNm maternels pendant la maturation de l’ovocyte .................................................. 26 La déadénylation des ARNm maternels pendant le développement embryonnaire ....................................... 26 2. Le clivage embryonnaire : du zygote au blastocyste ........................................................................................ 27 3. La transition materno-embryonnaire (MET) .................................................................................................... 29 II. La transcription chez les eucaryotes ............................................................................................. 30 1. Le mécanisme général de la transcription ........................................................................................................ 30 2. Illustration avec l’exemple de la transcription par l’ARN polymérase II chez les eucaryotes ........................... 31 3. La maturation des ARN .................................................................................................................................... 33 a. L’addition de la coiffe à l’extrémité 5’ .................................................................................................................. 33 b. La polyadénylation en 3’ ...................................................................................................................................... 33 c. L’épissage alternatif ............................................................................................................................................. 34 III. Régulation de la transcription ...................................................................................................... 36 1. La modulation de l’accessibilité à l’ADN ........................................................................................................... 36 2. Les séquences cis-régulatrices de l’ADN ........................................................................................................... 37 3. Le phénomène d’interférence d’ARN ................................................................................................................ 38 Zoom sur la régulation par les ARNmi .............................................................................................................. 40 IV. L’activation du génome embryonnaire ......................................................................................... 42 1. Le moment de l’activation : activations mineure et majeure ........................................................................... 42 2. Le contrôle de l’activation du génome embryonnaire ...................................................................................... 44 a. L’utilisation des protéines et des ARNm maternels stockés par l’ovocyte ............................................................. 44 b. Les modifications de la chromatine ...................................................................................................................... 45 La déméthylation de l’ADN ............................................................................................................................... 45 La répression de la transcription par la méthylation de l’ADN et son lien avec la modification des histones ........................................................................................................................................................................ 47 c. Le rôle de la réplication de l’ADN ......................................................................................................................... 48 3. La dégradation des transcrits maternels .......................................................................................................... 49 1 a. La voie de l’interférence....................................................................................................................................... 49 Chez le xénope, la souris .................................................................................................................................. 50 Chez les bovins ................................................................................................................................................. 51 b. Les protéines de liaison à l’ARN ........................................................................................................................... 52 c. L’autophagie ........................................................................................................................................................ 53 Chez la souris ...................................................................................................................................................
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