Genome-wide survey of D/E repeats in human proteins uncovers their instability and aids in identifying their role in the chromatin regulator ATAD2.
Genome-wide survey of D/E repeats in human proteins uncovers their instability and aids in identifying their role in the chromatin regulator ATAD2.
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DOI：
10.1016/j.isci.2022.105464
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发表时间：
2022-12-22
期刊：
影响因子：
5.8
通讯作者：
Sidorova, Julia M.
中科院分区：
文献类型：
--
作者：
Shukla, Shalabh;Lazarchuk, Pavlo;Pavlova, Maria N.;Sidorova, Julia M.
D/E重复序列是在超过150种人类蛋白质中发现的天冬氨酸和/或谷氨酸残基的延伸。我们研究了D/E重复序列的基因组稳定性和含有D/E重复序列的蛋白质相对维斯具有poly-Q或poly-A重复序列的蛋白质的功能特征，这些蛋白质已知会发生病理性扩增。肿瘤测序数据的挖掘显示，D/E重复编码区与编码多聚-Q和多聚-A的区域在三核苷酸插入/缺失的发生率增加方面相似，但在取代的类型和发生率方面不同。含有D/E重复序列的蛋白质优先在染色质代谢中起作用，并且它们的重复序列越长，越可能是核蛋白并与核心组蛋白相互作用。未知功能的最长D/E重复序列之一是ATAD 2，一种经常在肿瘤中过表达的溴结构域家族ATP酶。我们证明，D/E重复ATAD 2的缺失抑制其结合新生和成熟的染色质和组成性的着丝粒周围异染色质，ATAD 2抑制卫星转录。许多人类蛋白质含有天冬氨酸/谷氨酸残基（D/E重复序列）D/E重复序列显示肿瘤中框内插入/缺失的发生率增加核和组蛋白相互作用蛋白通常具有长D/E重复序列癌基因ATAD 2的D/E重复序列控制其与臂间染色质的结合生物化学;分子生物学;基因组学
D/E repeats are stretches of aspartic and/or glutamic acid residues found in over 150 human proteins. We examined genomic stability of D/E repeats and functional characteristics of D/E repeat-containing proteins vis-à-vis the proteins with poly-Q or poly-A repeats, which are known to undergo pathologic expansions. Mining of tumor sequencing data revealed that D/E repeat-coding regions are similar to those coding poly-Qs and poly-As in increased incidence of trinucleotide insertions/deletions but differ in types and incidence of substitutions. D/E repeat-containing proteins preferentially function in chromatin metabolism and are the more likely to be nuclear and interact with core histones, the longer their repeats are. One of the longest D/E repeats of unknown function is in ATAD2, a bromodomain family ATPase frequently overexpressed in tumors. We demonstrate that D/E repeat deletion in ATAD2 suppresses its binding to nascent and mature chromatin and to the constitutive pericentromeric heterochromatin, where ATAD2 represses satellite transcription. Many human proteins contain runs of aspartic/glutamic acid residues (D/E repeats) D/E repeats show increased incidence of in-frame insertions/deletions in tumors Nuclear and histone-interacting proteins often have long D/E repeats D/E repeat of the oncogene ATAD2 controls its binding to pericentric chromatin Biochemistry; Molecular biology; Genomics
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影响因子：
10.5
作者：
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富含谷氨酰胺的可变重复序列调节转录因子活性。
影响因子：
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作者：
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通讯作者：
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作者：
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