ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator

EMBO Reports
Arne JahnDennis Kappei

Abstract

Telomeres constitute the ends of linear chromosomes and together with the shelterin complex form a structure essential for genome maintenance and stability. In addition to the constitutive binding of the shelterin complex, other direct, yet more transient interactions are mediated by the CST complex and HOT1/HMBOX1, while subtelomeric variant repeats are recognized by NR2C/F transcription factors. Recently, the Kruppel-like zinc finger protein ZBTB48/HKR3/TZAP has been described as a novel telomere-associated factor in the vertebrate lineage. Here, we show that ZBTB48 binds directly both to telomeric and to subtelomeric variant repeat sequences. ZBTB48 is found at telomeres of human cancer cells regardless of the mode of telomere maintenance and it acts as a negative regulator of telomere length. In addition to its telomeric function, we demonstrate through a combination of RNAseq, ChIPseq and expression proteomics experiments that ZBTB48 acts as a transcriptional activator on a small set of target genes, including mitochondrial fission process 1 (MTFP1). This discovery places ZBTB48 at the interface of telomere length regulation, transcriptional control and mitochondrial metabolism.

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Citations

Jul 28, 2017·Cell Cycle·Filip ČervenákL'ubomír Tomáška
Feb 9, 2018·International Journal of Molecular Sciences·Kez ClealDuncan Baird
Nov 22, 2018·Nucleic Acids Research·Rongbin ZhengX Shirley Liu
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Datasets Mentioned

BETA
GSE96778
PXD006074

Methods Mentioned

BETA
immunoprecipitation
ChIPseq
PCR
electrophoresis
RNAseq
fluorescence microscopy
transfection
genotyping
ChIP
Assay

Software Mentioned

Ensembl
Python script
bigwig
DESeq2
Bowtie
featureCounts
Imaris
mfold
MEME
MaxQuant

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