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KAP-1 Corepressor Protein Interacts and Colocalizes with Heterochromatic and Euchromatic HP1 Proteins: a Potential Role for Krüppel-Associated Box–Zinc Finger Proteins in Heterochromatin-Mediated Gene Silencing 下载免费PDF全文
Robert F. Ryan David C. Schultz Kasirajan Ayyanathan Prim B. Singh Josh R. Friedman William J. Fredericks Frank J. Rauscher III 《Molecular and cellular biology》1999,19(6):4366-4378
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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