Synthetic Activation of Aberrantly Silenced Genes in Diseases

Diplôme Thèse Synthetic Activation of Aberrantly Silenced Genes in Diseases eng 2020-02-20 author Hafner Nicolas 834050 director Murr Rabih 827872 10.13097/archive-ouverte/unige:141767 urn:nbn:ch:unige-1417679 Sc. Vie 49 DNA methylation influences the accessibility of DNA to transcription factors (TFs). Aberrant hypermethylation and subsequent inhibition of tumor suppressor gene (TSG) promoters is a hallmark in many cancers. Reactivation of TSGs in cancer cells by targeted demethylation of their promoters is an attractive therapeutic approach. A recently identified class of TFs, called super pioneer factors (SPFs), can bind to methylated DNA, leading to demethylation. Here, we explore the possibility of reactivation of methylated promoters of TSGs, by recruitment of SPFs via CRISPR/Cas9-mediated insertion of their binding motifs. To find additional therapeutic targets for epigenome editing, we investigated the epigenetic profile of various adipose tissues. Here, we performed methylome and transcriptome analysis on visceral adipose tissue in mice after and before treatment with cold and antibiotics. Dewey 576.5 135 Département de médecine génétique et développement 21D false c3686adb-0914-4195-aa08-cb82a52d2e2f Thesis Public [NicolasHafner]_PhD_Thesis_Final.pdf 6885317 application/pdf openAccess Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

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Synthetic Activation of Aberrantly Silenced Genes in Diseases				2020	705	555

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Hafner, Nicolas