Abstract 1468: ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator

Abstract Telomeres consist of repetitive TTAGGG repeats and together with the shelterin complex protect the ends of linear chromosomes from DNA repair mechanisms. Due to telomere shortening with every cell division proliferating cells need to ensure telomere maintenance by telomerase or in about 15% of cancer cells via the recombination based alternative lengthening of telomeres. Recently ZBTB48 was identified as a novel telomere-associated factor throughout the vertebrate lineage. Here we show that ZBTB48 binds directly to telomeres in vitro and in vivo, independently of the telomere maintenance mechanism. Loss of the protein leads to longer telomeres indicating a role as negative regulator of telomere length. Furthermore RNAseq, ChIPseq and quantitative expression proteomics demonstrate a function as transcriptional activator for a small set of target genes, including mitochondrial fission process 1 (MTFP1). This regulatory role links its telomeric function to mitochondrial metabolism and might play a role in cancer development. In summary ZBTB48 is a novel telomere binding protein which regulates telomere length and transcriptional activity. Citation Format: Arne Jahn, Grishma Rane, Maciej Paszkowski-Rogacz, Sergi Sayols, Alina Bluhm, Chung-Ting Han, Irena Draškovič, Arturo Londoño, Alan Prem Kumar, Frank Buchholz, Falk Butter, Dennis Kappei. ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1468.