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Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [cutandtag]

ABSTRACT: Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [cutandtag]

PROVIDER: PRJNA1230089 | ENA |

REPOSITORIES: ENA

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Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [cutandtag]

Project description:The primate-restricted KRAB zinc finger protein (KZFP) ZNF93 represses a subset of L1 transposable elements (TEs) that propagated in the human ancestral genome some 20 to 12 million years ago and have all become transposition-incompetent due to inactivating mutations. Here, we demonstrate that these L1 integrants encode a highly genotoxic endonuclease, and that ZNF93 also represses other full-length L1 integrants via indirect effects as well as APOBEC3B. Consistent with the exquisite sensitivity of single-stranded DNA to attack by both the L1 endonuclease and the cytidine deaminase, ZNF93 expression peaks in S phase and correlates with cell proliferation. ZNF93 is induced in most cancers, and ZNF93-depleted cells exhibit defects in DNA synthesis and activation of the replication and DNA damage checkpoints. These results suggest a model whereby ZNF93 is a major guardian of genome integrity subverted by cancer cells to escape L1-mediated epigenetic surveillance and achieve a proper balance of APOBEC3B-induced tumor heterogeneity and overall genome stability.

2025-08-01 | GSE290773 | GEO

Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_2]

2025-08-01 | GSE290771 | GEO

Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_1]

2025-08-01 | GSE290770 | GEO

Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_3]

2025-08-01 | GSE290772 | GEO

Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B

Project description:Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B

| PRJNA1230070 | ENA

Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_1]

Project description:Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_1]

| PRJNA1230087 | ENA

Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_3]

Project description:Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_3]

| PRJNA1230088 | ENA

Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_2]

Project description:Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_2]

| PRJNA1230072 | ENA

Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B

Project description:This SuperSeries is composed of the SubSeries listed below.

2025-07-31 | GSE290774 | GEO

Mapping the genomic occupancy by flag-tagged APOBEC3B protein

Project description:Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3B) is a key molecular driver inducing mutations in multiple human cancers. APOBEC3B belongs to the APOBEC3 enzyme family, which consists seven closely related DNA deaminases that catalyse cytosine-to-uracil (C>U) editing of single-stranded DNA (ssDNA). In order to investigate the genomic binding sites of APOBEC3B, high through-put sequencing experiments were conducted using DNA samples acquired by standard chromatin immunoprecipitation (ChIP) and ssDNA protein immunoprecipitation (SPI) samples. Substrate preference by APOBEC3B were characterised by comparing these results.

2025-01-06 | GSE193227 | GEO

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