ZBTB10 binds the telomeric variant repeat TTGGGG and interacts with TRF2
ZBTB10 binds the telomeric variant repeat TTGGGG and interacts with TRF2
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DOI：
10.1093/nar/gky1289
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发表时间：
2019-02-28
影响因子：
14.9
通讯作者：
Butter, Falk
中科院分区：
文献类型：
--
作者：
Bluhm, Alina;Viceconte, Nikenza;Butter, Falk
端粒是线性染色体末端的核蛋白结构，是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，然而，在使用端粒选择性延长 (ALT) 机制的细胞中，变异重复序列散布在整个端粒中。此前，研究表明 NR2C/F 转录因子与 TCAGGG 变异重复序列结合，有助于 ALT 细胞中端粒的维持。虽然迄今为止还缺乏其他变异重复序列的特异性结合剂，但我们在此将 ZBTB10 鉴定为第一个 TTGGGG 结合蛋白，并证明通过两个锌指直接结合，亲和力在纳摩尔范围内。与此同时，ZBTB10 与 ALT 阳性 U2OS 细胞中的端粒子集共定位，并通过 TRF2 的 N 端区域与 TRF2/RAP1 相互作用。我们的数据表明 ZBTB10 是 ALT 端粒上的一种新型变异重复结合蛋白。
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.