ZBTB48

Last update 08 May 2025

Basic Info

Synonyms

HKR3, Krueppel-related zinc finger protein 3, Telomere zinc finger-associated protein

+ [6]

Introduction

Telomere-binding protein that acts as a regulator of telomere length (PubMed:28082411, PubMed:28500257). Directly binds the telomeric double-stranded 5'-TTAGGG-3' repeat (PubMed:28082411, PubMed:28500257). Preferentially binds to telomeres that have a low concentration of shelterin complex and acts as a regulator of telomere length by initiating telomere trimming, a process that prevents the accumulation of aberrantly long telomeres (PubMed:28082411). Also acts as a transcription regulator that binds to promoter regions (PubMed:24382891, PubMed:28500257, PubMed:7969177). Regulates expression of a small subset of genes, including MTFP1 (PubMed:28500257). Regulates expression the J and/or S elements in MHC II promoter (PubMed:7969177). Acts as a negative regulator of cell proliferation by specifically activating expression of ARF, a tumor suppressor isoform of CDKN2A (PubMed:24382891).

100 Clinical Results associated with ZBTB48

100 Translational Medicine associated with ZBTB48

0 Patents (Medical) associated with ZBTB48

Literatures (Medical) associated with ZBTB48

11 Jun 2023·bioRxiv : the preprint server for biology

Developmental transcriptional control of mitochondrial homeostasis is required for activity-dependent synaptic connectivity.

Author: Atak, Zeynep Kalender ; Corti, Olga ; Danda, Natasha ; Asfogo, Noemi ; Pascual-Caro, Carlos ; Bengochea, Mercedes ; De Waegeneer, Maxime ; Aerts, Stein ; Fonseca-Topp, Sara ; Preat, Thomas ; Mohylyak, Iryna ; Plaçais, Pierre-Yves ; de Juan-Sanz, Jaime ; Hassan, Bassem A

During neuronal circuit formation, local control of axonal organelles ensures proper synaptic connectivity. Whether this process is genetically encoded is unclear and if so, its developmental regulatory mechanisms remain to be identified. We hypothesized that developmental transcription factors regulate critical parameters of organelle homeostasis that contribute to circuit wiring. We combined cell type-specific transcriptomics with a genetic screen to discover such factors. We identified Telomeric Zinc finger-Associated Protein (TZAP) as a temporal developmental regulator of neuronal mitochondrial homeostasis genes, including Pink1 . In Drosophila , loss of dTzap function during visual circuit development leads to loss of activity-dependent synaptic connectivity, that can be rescued by Pink1 expression. At the cellular level, loss of dTzap/TZAP leads to defects in mitochondrial morphology, attenuated calcium uptake and reduced synaptic vesicle release in fly and mammalian neurons. Our findings highlight developmental transcriptional regulation of mitochondrial homeostasis as a key factor in activity-dependent synaptic connectivity.

01 Apr 2023·iScience

TZAP overexpression induces telomere dysfunction and ALT-like activity in ATRX/DAXX-deficient cells

Article

Author: Li, Julia Su Zhou ; Nassour, Joe ; Karlseder, Jan ; Kaiser, Melanie ; Denchi, Eros Lazzerini ; Haggblom, Candy ; Moreno, Sara Priego ; Fusté, Javier Miralles

The appropriate regulation of telomere length homeostasis is crucial for the maintenance of genome integrity. The telomere-binding protein TZAP has been suggested to regulate telomere length by promoting t-circle and c-circle excisions through telomere trimming, yet the molecular mechanisms by which TZAP functions at telomeres are not understood. Using a system based on TZAP overexpression, we show that efficient TZAP recruitment to telomeres occurs in the context of open telomeric chromatin caused by loss of ATRX/DAXX independently of H3.3 deposition. Moreover, our data indicate that TZAP binding to telomeres induces telomere dysfunction and ALT-like activity, resulting in the generation of t-circles and c-circles in a Bloom-Topoisomerase IIIα-RMI1-RMI2 (BTR)-dependent manner.

01 Dec 2022·Clinical Epigenetics

Genome-wide distribution of histone trimethylation reveals a global impact of bisphenol A on telomeric binding proteins and histone acetyltransferase factors: a pilot study with human and in vitro data

Article

Author: Fernandez, Mariana F ; Smagulova, Fatima ; Magnaghi-Jaulin, Laura ; Freire, Carmen ; Labussiere, Martin ; Hao, Chunxiang ; Legoff, Louis ; Rodriguez-Carrillo, Andrea ; Jaulin, Christian ; David, Arthur ; D'Cruz, Shereen Cynthia ; Mustieles, Vicente ; Olivas-Martinez, Alicia

AbstractObjectiveTo assess the genetic and epigenetic effects promoted by Bisphenol A (BPA) exposure in adolescent males from the Spanish INMA-Granada birth cohort, and in human cells.MethodsDNA methylation was analysed using MEDIP. Repeat number variation in genomic DNA was evaluated, along with the analysis of H3K4me3 by using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). Analyses were performed with material extracted from whole blood of the adolescents, complemented by in vitro assessments of human (HeLa) cells exposed to 10 nM BPA, specifically, immunofluorescence evaluation of protein levels, gene expression analysis and ChIP‒qPCR analysis.ResultsAdolescents in the high urinary BPA levels group presented a higher level of Satellite A (SATA) repetitive region copy numbers compared to those in the low BPA group and a tendency towards increase in telomere length. We also observed decreased DNA methylation at the promoters of the imprinted genesH19, KCNQ1,andIGF2; atLINE1retroelements; and at theARID2, EGFRandESRRAandTERTgenes. Genome-wide sequencing revealed increased H3K4me3 occupancy at the promoters of genes encoding histone acetyltransferases, telomeric DNA binding factors and DNA repair genes. Results were supported in HeLa cells exposed to 10 nM BPA in vitro. In accordance with the data obtained in blood samples, we observed higher H3K4me3 occupancy and lower DNA methylation at some specific targets in HeLa cells. In exposed cells, changes in the expression of genes encoding DNA repair factors (ATM, ARID2, TRP53) were observed, and increased expression of several genes encoding telomeric DNA binding factors (SMG7, TERT, TEN1, UPF1, ZBTB48) were also found. Furthermore, an increase in ESR1/ERa was observed in the nuclei of HeLa cells along with increased binding of ESR1 toKAT5, KMT2EandTERF2IPpromoters and decreased ESR1 binding at theRARApromoter. The DNA damage marker p53/TP53 was also increased.ConclusionIn this pilot study, genome-wide analysis of histone trimethylation in adolescent males exposed to BPA revealed a global impact on the expression of genes encoding telomeric binding proteins and histone acetyltransferase factors with similar results in HeLa cells. Nevertheless, larger studies should confirm our findings.

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ZBTB48

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