ZNF91

Last update 08 May 2025

Basic Info

Synonyms

HPF7, HTF10, zinc finger protein 91

+ [3]

Introduction

Transcription factor specifically required to repress SINE-VNTR-Alu (SVA) retrotransposons: recognizes and binds SVA sequences and represses their expression by recruiting a repressive complex containing TRIM28/KAP1 (PubMed:25274305). May also bind the promoter of the FCGR2B gene, leading to repress its expression; however, additional evidence is required to confirm this result in vivo (PubMed:11470777).

100 Clinical Results associated with ZNF91

100 Translational Medicine associated with ZNF91

0 Patents (Medical) associated with ZNF91

Literatures (Medical) associated with ZNF91

01 Oct 2024·Nature Structural & Molecular Biology

Mini-heterochromatin domains constrain the cis-regulatory impact of SVA transposons in human brain development and disease

Article

Author: Christoforidou, Georgia ; Jönsson, Marie E ; Castilla Vallmanya, Laura ; Karlsson, Ofelia ; Garza, Raquel ; Adami, Anita ; Douse, Christopher H ; Gerdes, Patricia ; Koutounidou, Symela ; Pandiloski, Ninoslav ; Johansson, Pia A ; Jakobsson, Johan ; Horváth, Vivien

AbstractSVA (SINE (short interspersed nuclear element)–VNTR (variable number of tandem repeats)–Alu) retrotransposons remain active in humans and contribute to individual genetic variation. Polymorphic SVA alleles harbor gene regulatory potential and can cause genetic disease. However, how SVA insertions are controlled and functionally impact human disease is unknown. Here we dissect the epigenetic regulation and influence of SVAs in cellular models of X-linked dystonia parkinsonism (XDP), a neurodegenerative disorder caused by an SVA insertion at the TAF1 locus. We demonstrate that the KRAB zinc finger protein ZNF91 establishes H3K9me3 and DNA methylation over SVAs, including polymorphic alleles, in human neural progenitor cells. The resulting mini-heterochromatin domains attenuate the cis-regulatory impact of SVAs. This is critical for XDP pathology; removal of local heterochromatin severely aggravates the XDP molecular phenotype, resulting in increased TAF1 intron retention and reduced expression. Our results provide unique mechanistic insights into how human polymorphic transposon insertions are recognized and how their regulatory impact is constrained by an innate epigenetic defense system.

13 Aug 2024·Proceedings of the National Academy of Sciences

ZNF91 is an endogenous repressor of the molecular phenotype associated with X-linked dystonia–parkinsonism (XDP)

Article

Author: Kapadia, Ashni ; Jacobs, Frank M. J. ; Farmiloe, Grace ; Raghib, Sanaz ; Bragg, D. Cristopher ; Brandorff, J. Elias ; Rosenkrantz, Jimi L. ; Vaine, Christine A.

X-linked dystonia–parkinsonism (XDP) is a severe neurodegenerative disorder resulting from an inherited intronic SINE-Alu-VNTR (SVA) retrotransposon in the TAF1 gene that causes dysregulation of TAF1 transcription. The specific mechanism underlying this dysregulation remains unclear, but it is hypothesized to involve the formation of G-quadruplexes (G4) structures within the XDP-SVA that impede transcription. In this study, we show that ZNF91, a critical repressor of SVA retrotransposons, specifically binds to G4-forming DNA sequences. Further, we found that genetic deletion of ZNF91 exacerbates the molecular phenotype associated with the XDP-SVA insertion in patient cells, while no difference was observed when ZNF91 was deleted from isogenic control cells. Additionally, we observed a significant age-related reduction in ZNF91 expression in whole blood and brain, indicating a progressive loss of repression of the XDP-SVA in XDP. These findings indicate that ZNF91 plays a crucial role in controlling the molecular phenotype associated with XDP. Since ZNF91 binds to G4-forming DNA sequences in SVAs, this suggests that interactions between ZNF91 and G4-forming sequences in the XDP-SVA minimize the severity of the molecular phenotype. Our results showing that ZNF91 expression levels significantly decrease with age provide a potential explanation for the age-related progressive neurodegenerative character of XDP. Collectively, our study provides important insights into the protective role of ZNF91 in XDP pathogenesis and suggests that restoring ZNF91 expression, destabilization of G4s, or targeted repression of the XDP-SVA could be future therapeutic strategies to prevent or treat XDP.

19 Jun 2023·Human molecular genetics

Lung adenocarcinoma cell-derived exosomes promote M2 macrophage polarization through transmission of miR-3153 to activate the JNK signaling pathway.

Article

Author: Wang, L ; Zhu, X ; Yang, R ; Li, T ; Xu, L

There is increasing evidence that exosome-mediated transmission of microRNAs helps to connect tumor-associated macrophages and cancer cells, including lung adenocarcinoma (LUAD) cells. The objective of this study is to identify the role of miR-3153 in LUAD progression and M2 macrophage polarization and explore its regulatory mechanism. The relevant molecular mechanisms were analyzed and validated through mechanistic assays. In vitro functional assays followed by in vivo experiments were implemented to evaluate the role of exosomes in mediating M2 macrophage polarization and LUAD progression. LUAD cells transmitted miR-3153 through exosomes. Heterogeneous nuclear ribonucleoprotein A2B1 promoted miR-3153 biosynthesis and exosomal sorting. Exosomal miR-3153 targeted zinc finger protein 91 to suppress the ubiquitination and degradation of misshapen-like kinase 1, thereby activating the c-Jun N-terminal kinase (JNK) signaling pathway and inducing M2 macrophage polarization. M2 macrophage polarization induced by LUAD cell-derived exosomes promoted the malignant process of LUAD cells. Transmission of exosomal miR-3153 by LUAD cells activates the JNK signaling pathway and induces M2 macrophage polarization, thus promoting the progression of LUAD.

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ZNF91

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