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KAP1 regulates endogenous retroviruses in adult human cells and contributes to innate immune control 下载免费PDF全文
Christopher HC Tie Liane Fernandes Lucia Conde Luisa Robbez‐Masson Rebecca P Sumner Tom Peacock Maria Teresa Rodriguez‐Plata Greta Mickute Robert Gifford Greg J Towers Javier Herrero Helen M Rowe 《EMBO reports》2018,19(10)
Endogenous retroviruses (ERVs) have accumulated in vertebrate genomes and contribute to the complexity of gene regulation. KAP1 represses ERVs during development by its recruitment to their repetitive sequences through KRAB zinc‐finger proteins (KZNFs), but little is known about the regulation of ERVs in adult tissues. We observed that KAP1 repression of HERVK14C was conserved in differentiated human cells and performed KAP1 knockout to obtain an overview of KAP1 function. Our results show that KAP1 represses ERVs (including HERV‐T and HERV‐S) and ZNF genes, both of which overlap with KAP1 binding sites and H3K9me3 in multiple cell types. Furthermore, this pathway is functionally conserved in adult human peripheral blood mononuclear cells. Cytosine methylation that acts on KAP1 regulated loci is necessary to prevent an interferon response, and KAP1‐depletion leads to activation of some interferon‐stimulated genes. Finally, loss of KAP1 leads to a decrease in H3K9me3 enrichment at ERVs and ZNF genes and an RNA‐sensing response mediated through MAVS signaling. These data indicate that the KAP1‐KZNF pathway contributes to genome stability and innate immune control in adult human cells. 相似文献
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Pycnidiospores of Phyllosticta ampelicida, the causal agent of black rot of grape, were found to germinate only on substrata on which they were firmly attached. Such surfaces were poorly wettable and had advancing contact angles (straight thetaa) formed by a water drop of >80°, e.g., grape leaf, polystyrene, Teflon, polycarbonate, collodion, and glass treated with the silanes n-octadecyltrichlorosilane, dimethyldichlorosilane, or diphenyldichlorosilane. When pycnidiospores were deposited on more wettable surfaces they did not attach firmly and did not germinate. Such highly wettable surfaces had straight thetaa = 40° and were represented by heat-treated glass, cellophane, nutrient- and water-agars, polystyrene treated with UV-irradiation or sulfuric acid, and glass silanized with n-2-aminoethyl-3-aminopropyltrimethoxysilane, n-(trimethoxysilylpropyl)ethylenediamine triacetic acid trisodium, or 3-aminopropyltriethoxysilane. Adhesion of pycnidiospores was assessed with and without a hydraulic shearing force. Pycnidiospore adhesion occurred over several minutes in distilled deionized water, unless it was first acidified, which decreased attachment time to <0.03 s. Attachment of pycnidiospores treated with sodium azide, formaldehyde, or boiled in water for 10 min was similar to nontreated conidia. Possible mechanisms of adhesion of the conidia to surfaces include hydrophobic and ionic interactions. 相似文献
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