Shelterin and subtelomeric DNA sequences control nucleosome maintenance and genome stability
Shelterin and subtelomeric DNA sequences control nucleosome maintenance and genome stability
复制标题
DOI：
10.15252/embr.201847181
复制
发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Thomas van Emden;Marta Forn;I. Forné;Zsuzsa Sarkadi;Matías Capella;Lucía Martín Caballero;Sabine Fischer-Burkart;Cornelia Brönner;M. Simonetta;D. Toczyski;M. Halić;A. Imhof;Sigurd Braun
中科院分区：
文献类型：
--
作者：
Thomas van Emden;Marta Forn;I. Forné;Zsuzsa Sarkadi;Matías Capella;Lucía Martín Caballero;Sabine Fischer-Burkart;Cornelia Brönner;M. Simonetta;D. Toczyski;M. Halić;A. Imhof;Sigurd Braun
端粒和庇护蛋白复合物盖住并保护染色体的末端。端粒两侧的亚端粒序列也与端粒调控有关，尽管它们的作用还没有很好地定义。本研究表明，在裂糖菌中，存在于大多数亚端粒上的端粒相关序列（TAS）是高度重组的，具有亚稳态核小体和异常低水平的H3K9甲基化。Ccq1是一个庇护亚基，通过募集异色抑制复合物CLRC和SHREC来保护TAS免受核小体的损失，从而将核小体的稳定性与基因沉默联系起来。TAS核小体的不稳定性与端粒重复序列无关，可以传递到含有异位TAS片段的染色体内位点，表明这是潜在DNA序列的内在特性。当端粒酶募集在缺乏Ccq1的细胞中受损时，TAS中存在的DNA序列促进染色体末端之间的重组，而不依赖于核小体的丰度，这意味着这些序列在端粒维持中具有活性功能。我们认为Ccq1和脆弱的亚端粒共同进化，通过控制核小体的占用和基因组的稳定性来调节端粒的可塑性。
Telomeres and the shelterin complex cap and protect the ends of chromosomes. Telomeres are flanked by the subtelomeric sequences that have also been implicated in telomere regulation, although their role is not well defined. Here we show that, in Schizosaccharomyces pombe, the telo-mere-associated sequences (TAS) present on most subtelomeres are hyper-recombinogenic, have metastable nucleosomes, and unusual low levels of H3K9 methylation. Ccq1, a subunit of shelter-in, protects TAS from nucleosome loss by recruiting the heterochromatic repressor complexes CLRC and SHREC, thereby linking nucleosome stability to gene silencing. Nucleosome instability at TAS is independent of telomeric repeats and can be transmitted to an intrachromosomal locus containing an ectopic TAS fragment, indicating that this is an intrinsic property of the underlying DNA sequence. When telomerase recruitment is compromised in cells lacking Ccq1, DNA se-quences present in the TAS promote recombination between chromosomal ends, independent of nucleosome abundance, implying an active function of these sequences in telomere maintenance. We propose that Ccq1 and fragile subtelomeres co-evolved to regulate telomere plasticity by con-trolling nucleosome occupancy and genome stability.