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ZBTB 48 is both a vertebrate telomere‐binding protein and a transcriptional activator
Author(s) -
Jahn Arne,
Rane Grishma,
PaszkowskiRogacz Maciej,
Sayols Sergi,
Bluhm Alina,
Han ChungTing,
Draškovič Irena,
LondoñoVallejo José Arturo,
Kumar Alan Prem,
Buchholz Frank,
Butter Falk,
Kappei Dennis
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201744095
Subject(s) - telomere , biology , shelterin , activator (genetics) , zinc finger , subtelomere , telomere binding protein , genetics , transcription factor , microbiology and biotechnology , gene , transcription (linguistics) , dna binding protein , linguistics , philosophy
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 HOT 1/ HMBOX 1, while subtelomeric variant repeats are recognized by NR 2C/F transcription factors. Recently, the Kruppel‐like zinc finger protein ZBTB 48/ HKR 3/ TZAP has been described as a novel telomere‐associated factor in the vertebrate lineage. Here, we show that ZBTB 48 binds directly both to telomeric and to subtelomeric variant repeat sequences. ZBTB 48 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 RNA seq, Ch IP seq and expression proteomics experiments that ZBTB 48 acts as a transcriptional activator on a small set of target genes, including mitochondrial fission process 1 ( MTFP 1). This discovery places ZBTB 48 at the interface of telomere length regulation, transcriptional control and mitochondrial metabolism.