Telomeres are nucleoprotein structures at the ends of linear chromosomes and present an essential feature for genome integrity. Vertebrate telomeres usually consist of hexameric TTAGGG repeats, however, in cells that use the alternative lengthening of telomeres (ALT) mechanism, variant repeat sequences are interspersed throughout telomeres. Previously, it was shown that NR2C/F transcription factors bind to TCAGGG variant repeats and contribute to telomere maintenance in ALT cells. While specific binders to other variant repeat sequences have been lacking to date, we here identify ZBTB10 as the first TTGGGG-binding protein and demonstrate direct binding via the two zinc fingers with affinity in the nanomolar range. Concomitantly, ZBTB10 co-localizes with a subset of telomeres in ALT-positive U2OS cells and interacts with TRF2/RAP1 via the N-terminal region of TRF2. Our data establishes ZBTB10 as a novel variant repeat binding protein at ALT telomeres.

译文

:端粒是线性染色体末端的核蛋白结构,具有基因组完整性的重要特征。脊椎动物端粒通常由六聚体TTAGGG重复序列组成,但是,在使用端粒交替延长(ALT)机制的细胞中,变异重复序列散布在整个端粒中。以前,已显示NR2C / F转录因子与TCAGGG变体重复结合并有助于ALT细胞中端粒的维持。尽管迄今为止还缺乏针对其他变异重复序列的特异性结合物,但我们在这里将ZBTB10确定为第一个TTGGGG结合蛋白,并证明通过两个锌指直接结合,其亲和力在纳摩尔范围内。同时,ZBTB10与ALT阳性U2OS细胞中的一部分端粒共定位,并通过TRF2的N端区域与TRF2 / RAP1相互作用。我们的数据将ZBTB10建立为ALT端粒的新型变异重复结合蛋白。

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