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Rôles de TFIIH dans l’ouverture du promoteur et le remodelage de la chromatine lors la transcription des gènes de classe II

Abstract : The synthesis of messenger RNA is a highly regulated process. During transcription initiation, a large number of proteins are recruited to gene promoter including RNA polymerase II, general transcription factors like TFIIH, co-activators and chromatin remodelers. The assembly of pre-initiation complex on promoters is followed by their opening. Accepted models to date suggested that transcription of class II genes requires TFIIH XPB subunit ATPase and helicase activities to actively open the promoter. However, we have observed that mRNA expression is compatible with the absence of XPB but requires its ATPase activity. These observations are consistent with an alternative model in which the ATPase activity of XPB is used to translocate the protein upstream of the initiation site, alleviating a block, imposed by the presence of XPB, of the promoter opening. Moreover, we found a new role for TFIIH in chromatin remodeling during transcription initiation. We highlighted a tight connection between TFIIH and the histone acetyltransferase KAT2A that controls higher-order chromatin structure and gene expression and provide new insights into transcriptional misregulation in combined Xeroderma Pigmentosum and Cockayne syndrome, a cancer-prone DNA repair-deficient disorder.
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Submitted on : Friday, December 13, 2019 - 9:43:11 AM
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Jérémy Sandoz. Rôles de TFIIH dans l’ouverture du promoteur et le remodelage de la chromatine lors la transcription des gènes de classe II. Biochimie, Biologie Moléculaire. Université de Strasbourg, 2019. Français. ⟨NNT : 2019STRAJ027⟩. ⟨tel-02408585⟩

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