ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma

Pieraccioli, Marco; Nicolai, Sara; Pitolli, Consuelo; Agostini, Massimiliano; Антонов, А.; Malewicz, Michal; Knight, Richard; Raschellà, Giuseppe; Melino, Gerry

doi:10.1073/pnas.1801435115

Cited by 43 publications

(37 citation statements)

References 27 publications

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“…Consequently, depletion of ZNF281 impairs the efficiency of the NHEJ repair pathway and decreases cell viability upon DNA damage. Survival analyses from datasets of commonly occurring human cancers, show that high levels of ZNF281 correlate with poor prognosis of patients treated with DNA-damaging therapies [36]. In conclusion Melino's lab results define a late ZNF281-dependent regulatory step of NHEJ complex assembly at DNA lesions supporting its additional role as marker for cancer patients' stratification for therapeutic approaches in NB treatment.…”

Section: Session III Functional Genomics In Clinical Practicementioning

confidence: 83%

From single gene analysis to single cell profiling: a new era for precision medicine

Martino

Meschini²,

Scotlandi

et al. 2020

J Exp Clin Cancer Res

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Molecular profiling of DNA and RNA has provided valuable new insights into the genetic basis of non-malignant and malignant disorders, as well as an increased understanding of basic mechanisms that regulate human disease. Recent technological advances have enabled the analyses of alterations in gene-based structure or function in a comprehensive, high-throughput fashion showing that each tumor type typically exhibits distinct constellations of genetic alterations targeting one or more key cellular pathways that regulate cell growth and proliferation, evasion of the immune system, and other aspects of cancer behavior. These advances have important implications for future research and clinical practice in areas as molecular diagnostics, the implementation of gene or pathwaydirected targeted therapy, and the use of such information to drive drug discovery. The 1st international and 32nd Annual Conference of Italian Association of Cell Cultures (AICC) conference wanted to offer the opportunity to match technological solutions and clinical needs in the era of precision medicine.

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Section: Session III Functional Genomics In Clinical Practicementioning

confidence: 83%

From single gene analysis to single cell profiling: a new era for precision medicine

Martino

Meschini²,

Scotlandi

et al. 2020

J Exp Clin Cancer Res

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“…These diverse TF clusters also included motifs for the SRY-related protein, SOX2, and the zinc finger nuclease (ZnF), ZNF281, which contribute toward the multipotent state of NPCs ( Fig. 6 ) ( 73 , 74 ). Interestingly, one +A DAR cluster included TFs in the nBAF (BCL11A), IRF (IRF3) and ETS (ETS2) protein families, which have defined roles outside of neuronal development ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic and epigenomic dynamics associated with development of human iPSC-derived GABAergic interneurons

Inglis

Zhou

Patterson

et al. 2020

Human Molecular Genetics

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GABAergic interneurons (GINs) are a heterogeneous population of inhibitory neurons that collectively contribute to the maintenance of normal neuronal excitability and network activity. Identification of the genetic regulatory elements and transcription factors that contribute toward GIN function may provide new insight into the pathways underlying proper GIN activity, while also indicating potential therapeutic targets for GIN-associated disorders, such as schizophrenia and epilepsy. In this study, we examined temporal changes in gene expression and chromatin accessibility during GIN development by performing transcriptomic and epigenomic analyses on human iPSC-derived neurons at 22, 50 and 78 days (D) post-differentiation. We observed 13 221 differentially accessible regions (DARs) of chromatin that associate with temporal changes in gene expression at D78 and D50, relative to D22. We also classified families of transcription factors that are increasingly enriched at DARs during differentiation, indicating regulatory networks that likely drive GIN development. Collectively, these data provide a resource for examining the molecular networks regulating GIN functionality.

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“…In addition, ZNF281 induces epithelial-mesenchymal transition (EMT) in tumour cells and controls the expression of several key EMT-associated genes [16]. Furthermore, in our previous studies, we found that ZNF281 antagonises the differentiation of murine cortical neurons and neuroblastoma cells [17] and that it is indirectly involved in the DDR, promoting the expression of several DDR genes in response to DNA-damaging drugs [18]. However, the role of ZNF281 within the DDR remains largely uncharacterised and poorly understood.…”

Section: Introductionmentioning

confidence: 87%

ZNF281 is recruited on DNA breaks to facilitate DNA repair by non-homologous end joining

et al. 2019

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Efficient repair of DNA double-strand breaks (DSBs) is of critical importance for cell survival. Although non-homologous end joining (NHEJ) is the most used DSBs repair pathway in the cells, how NHEJ factors are sequentially recruited to damaged chromatin remains unclear. Here, we identify a novel role for the zinc-finger protein ZNF281 in participating in the ordered recruitment of the NHEJ repair factor XRCC4 at damage sites. ZNF281 is recruited to DNA lesions within seconds after DNA damage through a mechanism dependent on its DNA binding domain and, at least in part, on poly-ADP ribose polymerase (PARP) activity. ZNF281 binds XRCC4 through its zinc-finger domain and facilitates its recruitment to damaged sites. Consequently, depletion of ZNF281 impairs the efficiency of the NHEJ repair pathway and decreases cell viability upon DNA damage. Survival analyses from datasets of commonly occurring human cancers show that higher levels of ZNF281 correlate with poor prognosis of patients treated with DNA-damaging therapies. Thus, our results define a late ZNF281-dependent regulatory step of NHEJ complex assembly at DNA lesions and suggest additional possibilities for cancer patients’ stratification and for the development of personalised therapeutic strategies.

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ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma

Cited by 43 publications

References 27 publications

From single gene analysis to single cell profiling: a new era for precision medicine

From single gene analysis to single cell profiling: a new era for precision medicine

Transcriptomic and epigenomic dynamics associated with development of human iPSC-derived GABAergic interneurons

ZNF281 is recruited on DNA breaks to facilitate DNA repair by non-homologous end joining

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