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Regulation of the human fibrinogen gene cluster through chromatin interactions

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Defense Thèse de doctorat : Univ. Genève, 2018 - Sc. 5261 - 2018/10/17
Abstract The coordinately regulated genes encoding human fibrinogen are clustered. The cluster is flanked by CCCTC-binding factor (CTCF) interaction sites that are candidate insulator regions mediating chromatin looping. We aimed to investigate whether interactions exist between parts of the fibrinogen locus and how these contacts contribute to fibrinogen expression. We used chromosome conformation capture to detect chromatin interactions at the fibrinogen gene cluster. We generated clonal cell lines where two CTCF sites at one end of the locus were deleted using CRISPR-Cas9. We detected proximity between the ends of the fibrinogen locus, regardless of whether cells express fibrinogen. Deletion of a CTCF site at one edge of the cluster altered chromatin interactions, reduced mRNA levels, and led to a halving of secreted fibrinogen. These phenotypes were completely restored by reintroduction of the CTCF interaction motif in previously motif-deleted clones. Chromatin interactions are important for the coordinated regulation of human fibrinogen genes.
Keywords FibrinogenGene regulationCCCTC-binding factorCRISPR-Cas9
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URN: urn:nbn:ch:unige-1109261
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ESPITIA JAIMES, Cindy. Regulation of the human fibrinogen gene cluster through chromatin interactions. Université de Genève. Thèse, 2018. https://archive-ouverte.unige.ch/unige:110926

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Deposited on : 2018-11-19

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