ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator.
ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator.
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DOI：
10.15252/embr.201744095
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发表时间：
2017-06
期刊：
影响因子：
7.7
通讯作者：
Kappei D
中科院分区：
文献类型：
--
作者：
Jahn A;Rane G;Paszkowski-Rogacz M;Sayols S;Bluhm A;Han CT;Draškovič I;Londoño-Vallejo JA;Kumar AP;Buchholz F;Butter F;Kappei D
端粒构成线性染色体的末端，并与shelterin复合物一起形成基因组维持和稳定所必需的结构。除了shelterin复合物的组成性结合，其他直接的，但更短暂的相互作用是由CST复合物和HOT 1/HMBOX 1介导的，而亚端粒变异重复序列被NR 2C/F转录因子识别。最近，Kruppel样锌指蛋白ZBTB 48/HKR 3/TZAP已被描述为脊椎动物谱系中的一种新型端粒相关因子。在这里，我们表明，ZBTB 48直接结合到端粒和亚端粒变异重复序列。ZBTB 48存在于人类癌细胞的端粒处，而不管端粒维持的模式如何，并且其充当端粒长度的负调节剂。除了其端粒功能外，我们还通过RNAseq，ChIPseq和表达蛋白质组学实验的组合证明ZBTB 48在一小部分靶基因上充当转录激活因子，包括线粒体裂变过程1（MTFP 1）。这一发现将ZBTB 48置于端粒长度调节、转录控制和线粒体代谢的界面。
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.