ZNF395 Is an Activator of a Subset of IFN-Stimulated Genes

Abstract

Activation of the interferon (IFN) pathway in response to infection with pathogens results in the induction of IFN-stimulated genes (ISGs) including proinflammatory cytokines, which mount the proper antiviral immune response. However, aberrant expression of these genes is pathogenic to the host. In addition to IFN-induced transcription factors non-IFN-regulated factors contribute to the transcriptional control of ISGs. Here, we show by genome wide expression analysis, siRNA-mediated suppression and Doxycycline-induced overexpression that the cellular transcription factor ZNF395 activates a subset of ISGs including the chemokines CXCL10 and CXCL11 in keratinocytes. We found that ZNF395 acts independently of IFN but enhances the IFN-induced expression of CXCL10 and CXCL11. Luciferase reporter assays revealed a requirement of intact NFκB-binding sites for ZNF395 to stimulate the CXCL10 promoter. The transcriptional activation of CXCL10 and CXCL11 by ZNF395 was abolished after inhibition of IKK by BMS-345541, which increased the stability of ZNF395. ZNF395 encodes at least two motifs that mediate the enhanced degradation of ZNF395 in response to IKK activation. Thus, IKK is required for ZNF395-mediated activation of transcription and enhances its turn-over to keep the activity of ZNF395 low. Our results support a previously unrecognized role of ZNF395 in the innate immune response and inflammation.

VIRdb 2.0: Interactive analysis of comorbidity conditions associated with vitiligo pathogenesis using co-expression network-based approach

“…With the aid of statistical procedures, we found significant DEGs that show correlated expressions in vitiligo, PS, MS and RA. ZNF395 which activates a subset of ISGs including the chemokines CXCL10 and CXCL11 in keratinocytes was co-expressed between the PS and vitiligo 38 . CXCL10 and CXCL11, are expressed in skin keratinocytes and are involved in the development of proinflammatory skin diseases such as vitiligo 38 .…”

“…ZNF395 which activates a subset of ISGs including the chemokines CXCL10 and CXCL11 in keratinocytes was co-expressed between the PS and vitiligo 38 . CXCL10 and CXCL11, are expressed in skin keratinocytes and are involved in the development of proinflammatory skin diseases such as vitiligo 38 . ZNF395 was over-expressed in our dataset of positively co-expressed DEGs from vitiligo samples and was underexpressed in samples of PS (Extended data, Appendix-III 19 ).…”

Comparative transcriptome analysis reveals the role of p53 signalling pathway during red‐spotted grouper nervous necrosis virus infection in Lateolabrax japonicus brain cells

“…Zinc finger protein 395 (ZNF395) is one of the most down‐regulated genes (decreased by 18.11 times) in this study. ZNF395, as a novel hypoxia‐inducible transcription factor, contributes to the maximal stimulation of a subset of ISGs, such as ISG15, IFIT1/ISG56, IFI44, CXCL10 and CXCL11 (Schroeder, Herwartz, Jordanovski, & Steger, ). In this study, in line with the down‐regulation of ISG15 , the expression of ZNF395 was also decreased.…”

Dysregulation of Zinc Finger Protein 395 Contributes to the Pathogenesis of Chondrosarcoma

“…The primers for ZNF395 were followed as Forward: 5ʹ- CGAAAAAAGAAAGAACTCTGTG-3ʹ; Reverse: 5ʹ- CTGTGTCCCCCCAGATGGAG-3ʹ as described previously. 22 The PCR amplification for the quantification of the ZNF395 mRNAs was performed using the SYBR green mix (Applied Biosystems) with a 7500 Fast Real-Time PCR System (Applied Biosystems) as described in our previous studies. 23 …”