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RNA-seq of ZNF417/ZNF587 KD or control H1 cells

ABSTRACT: RNAseq of human embryonic stem cells depleted for ZNF417 and ZNF587 or control cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE144153 | GEO | 2020/01/24

REPOSITORIES: GEO

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ChIP-seq on Znf417 and Znf587 overexpression 293T to verify Znf417 and Znf587 binding capacity at PBS-Lys elements.

Project description:The ChIP-seq experiments using GFP antibody on ZNF417/ZNF587-GFP overexpressing 293T cells revealed that ZNF417/ZNF587 preferred to bind a PBS-Lys-containing HERVs. Further motif calling analysis showed that both ZNF417 and ZNF587 bind to HERVK PBS-resembled motif.

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RNA-seq of ZNF417/ZNF587 KD or control H1 cells

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RNA-seq on ZNF417/587 double KO K562

Project description:To verify ZNF417 and ZNF587 knock out whether leads to HERV-K element reactivation, we performed RNA-seq on ZNF417/ZNF587 double knock out (DKO) K562 cell lines. We observed a dozen of genes were upregulated in KO cells, and some of them possessed PBS-Lys sites near their promoters that can be directly targeted by ZNF417 and ZNF587, such as MS4A clusters. We also measured the expression levels of repetitive elements in ZNF417 ZNF587 dKO cells, which exhibited only some ERVs reactivation indirectly.

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RNA-seq on ZNF417/587 double KO 293T

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Project description:The role of Krüppel-associated box zinc finger proteins (KZFPs), the largest family of repressive transcription factors (TFs) of the human genome, in the pathogenesis of diffuse large B cell lymphoma has not been addressed so far. By correlating the expression of KZFPs with patient outcome, we delineated a subset of 18 co-expressed KZFPs associated to poor prognosis, higher copy number alterations (CNA), and the suppression of hallmarks gene sets linked to immune rejection. Among them, the depletion of the ZNF587-ZNF417 pair of TF paralogs drastically impaired the proliferation of both activated B cell (ABC) and germinal center B (GCB) DLBCL cell lines, by triggering replicative stress through the awakening of dormant replication origins and profound alterations of the heterochromatin landscape. ZNF587/417 knockdown profoundly altered the transcriptomic landscape of U2932 (ABC) and OCI-Ly7 (GCB) cells, rewiring gene expression networks associated with good prognosis and upregulating interferon (IFN)/inflammatory-related genes through activation of the cGAS-STING DNA sensing pathway. These cells showed signs of altered immunogenicity with an enhanced MHC class I surface expression and a reshuffling of their immunopeptidome. Our study provides evidence that the ZNF587-ZNF417 paralog pair may promote lymphoma growth, the acquisition of genetic diversity, and its immune evasion by preventing excessive replicative stress. This suggests that these TFs participate in the epigenetic memory of lymphoma cells, thus highlighting the critical role of constitutive heterochromatin in maintaining the identity of poor-prognosis DLBCL.

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Integration sites sequencing of HIV infection on ZNF417 ZNF587 dKO 293T cells

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